Vascular plants contain two gene families that encode monosaccharide transporter proteins. The classical monosaccharide transporter（-like） gene superfamily is large and functionally diverse, while the recently ident...Vascular plants contain two gene families that encode monosaccharide transporter proteins. The classical monosaccharide transporter（-like） gene superfamily is large and functionally diverse, while the recently identified SWEET transporter family is smaller and, thus far, only found to transport glucose. These transporters play essential roles at many levels, ranging from organelles to the whole plant. Many family members are essential for cellular homeostasis and reproductive success. Although most transporters do not directly participate in long-distance transport, their indirect roles greatly impact carbon allocation and transport flux to the heterotrophic tissues of the plant. Functional characterization of some members from both gene families has revealed their diverse roles in carbohydrate partitioning, phloem function, resource allocation, plant defense, and sugar signaling. This review highlights the broad impacts and implications of monosaccharide transport by describing some of the functional roles of the monosaccharide transporter（-like） superfamily and the SWEET transporter family.展开更多
Salinity is one of the major abiotic stresses which impose constraints to plant growth and production.Rice(Oryza sativa L.)is one of the most important staple food crops and a model monocot plant.Its production is exp...Salinity is one of the major abiotic stresses which impose constraints to plant growth and production.Rice(Oryza sativa L.)is one of the most important staple food crops and a model monocot plant.Its production is expanding into regions that are affected by soil salinity,requiring cultivars more tolerant to saline conditions.Understanding the molecular mechanisms of such tolerance could lay a foundation for varietal improvement of salt tolerance in rice.In spite of extensive studies exploring the mechanism of salt tolerance,there has been limited progress in breeding for increased salinity tolerance.In this review,we summarize the information about the major molecular mechanisms underlying salinity tolerance in rice and further discuss the limitations in breeding for salinity tolerance.We show that numerous gene families and interaction networks are involved in the regulation of rice responses to salinity,prompting a need for a comprehensive functional analysis.We also show that most studies are based on whole-plant level analyses with only a few reports focused on tissue-and/or cell-specific gene expression.More details of salt-responsive channel and transporter activities at tissue-and cell-specific level still need to be documented before these traits can be incorporated into elite rice germplasm.Thus,future studies should focus on diversity of available genetic resources and,particular,wild rice relatives,to reincorporate salinity tolerance traits lost during domestication.展开更多
Proplastids are undifferentiated plastids of meristematic tissues that synthesize amino acids for protein synthesis, fatty acids for membrane lipid production, and purines and pyrimidines for DNA and RNA synthesis. Un...Proplastids are undifferentiated plastids of meristematic tissues that synthesize amino acids for protein synthesis, fatty acids for membrane lipid production, and purines and pyrimidines for DNA and RNA synthesis. Unlike chloroplasts, proplastids depend on supply, with reducing power, energy, and precursor metabolites from the remainder of the cell. Comparing proplastid and chloroplast envelope proteomes and the corresponding transcriptomes of leaves and shoot apex revealed a clearly distinct composition of the proplastid envelope. It is geared towards import of metabolic precursors and export of product metabolites for the rapidly dividing cell. The analysis also suggested a new role for the triosephosphate translocator in meristematic tissues, identified the route of organic nitrogen import into proplastids, and detected an adenine nucleotide exporter. The protein import complex contains the import receptors Toc120 and Toc132 and lacks the redox sensing complex subunits of Tic32, Tic55, and Tic62, which mirrors the expression patterns of the corresponding genes in leaves and the shoot apex. We further show that the protein composition of the internal membrane system is similar to etioplasts, as it is dominated by the ATP synthase complex and thus remarkably differs from that of chloroplast thylakoids.展开更多
Due to the presence of plastids, eukaryotic photosynthetic cells represent the most highly compartmentalized eukaryotic cells. This high degree of compartmentation requires the transport of solutes across intracellula...Due to the presence of plastids, eukaryotic photosynthetic cells represent the most highly compartmentalized eukaryotic cells. This high degree of compartmentation requires the transport of solutes across intracellular membrane systems by specific membrane transporters. In this review, we summarize the recent progress on functionally characterized intracellular plant membrane transporters and we link transporter functions to Arabidopsis gene identifiers and to the transporter classification system. In addition, we outline challenges in further elucidating the plant membrane permeome and we provide an outline of novel approaches for the functional characterization of membrane transporters.展开更多
Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly co...Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly controlled at multiple levels. It has been clearly shown that cholesterol redistribution and depletion from the sperm membrane is a key part of the spermatozoon＇s preparation for fertilization. Some factors that regulate these events are described （e.g., bicarbonate, calcium） but the mechanisms underlying cholesterol export are poorly understood. How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings？ This review will provide an overview of knowledge in this area and highlight our gaps in understanding. The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors. Armed with such knowledlze, sl）erm handlin~ techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.展开更多
The plant sucrose transporter SUT1 （from Solanum tuberosum, S. lycopersicum, or Zea mays） exhibits redoxdependent dimerization and targeting if heterologously expressed in S. cerevisiae （Krtigel et al., 2008）. It ...The plant sucrose transporter SUT1 （from Solanum tuberosum, S. lycopersicum, or Zea mays） exhibits redoxdependent dimerization and targeting if heterologously expressed in S. cerevisiae （Krtigel et al., 2008）. It was also shown that SUT1 is present in motile vesicles when expressed in tobacco cells and that its targeting to the plasma membrane is reversible. StSUT1 is internalized in the presence of brefeldin A （BFA） in yeast, plant cells, and in mature sieve elements as confirmed by immunolocalization. These results were confirmed here and the dynamics of intracellular SUT1 localization were further elucidated. Inhibitor studies revealed that vesicle movement of SUT1 is actin-dependent. BFA-mediated effects might indicate that anterograde vesicle movement is possible even in mature sieve elements, and could involve components of the cytoskeleton that were previously thought to be absent in SEs. Our results are in contradiction to this old dogma of plant physiology and the potential of mature sieve elements should therefore be re-evaluated. In addition, SUT1 internalization was found to be dependent on the plasma membrane lipid composition. SUT1 belongs to the detergent-resistant membrane （DRM） fraction in planta and is targeted to membrane raft-like microdomains when expressed in yeast （Kr（igel et al,, 2008）, Here, SUT1-GFP expression in different yeast mutants, which were unable to perform en- docytosis and/or raft formation, revealed a strong link between SUT1 raft localization, the sterol composition and mem- brane potential of the yeast plasma membrane, and the capacity of the SUT1 protein to be internalized by endocytosis. The results provide new insight into the regulation of sucrose transport and the mechanism of endocytosis in plant cells.展开更多
GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address th...GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address the question, first, 5’ Rapid amplification of cDNA end (RACE) was used to determine GAT1 transcriptional starting sites in neonatal mouse cerebral cortex and intestine, adult mouse brain and adult rat testis. The products of 5’RACE were confirmed by DNA sequencing. We found that the transcript of GAT1 in neonatal mouse cerebral cortex and adult mouse brain starts at the same site (inside of exon 1), while in mouse intestine, GAT1 starts transcription in intron 1, and in rat testis, the transcript of GAT1 has an additional untranslation exon to the 5’ direction.展开更多
The Major Facilitator Superfamily(MFS)is ubiquitous in living organisms and represents the largest group of secondary active membrane transporters.In plants,significant research efforts have focused on the role of spe...The Major Facilitator Superfamily(MFS)is ubiquitous in living organisms and represents the largest group of secondary active membrane transporters.In plants,significant research efforts have focused on the role of specific families within the MFS,particularly those transporting macronutrients(C,N,and P)that constitute the vast majority of the members of this superfamily.Other MFS families remain less explored,although a plethora of additional substrates and physiological functions have been uncovered.Nevertheless,the lack of a systematic approach to analyzing the MFS as a whole has obscured the high diversity and versatility of these transporters.Here,we present a phylogenetic analysis of all annotated MFS domaincontaining proteins encoded in the Arab/dops/s fA?a//ana genome and propose that this superfamily of transporters consists of 218 members,clustered in 22 families.In reviewing the available information regarding the diversity in biological functions and substrates of Arab/dops/s MFS members,we provide arguments for intensified research on these membrane transporters to unveil the breadth of their physiological relevance,disclose the molecular mechanisms underlying their mode of action,and explore their biotechnological potential.展开更多
Replicating extraordinarily high membrane transport selectivity of protein channels in artificial channel is a challenging task.In this work,we demonstrate that a strategic application of steric code-based social self...Replicating extraordinarily high membrane transport selectivity of protein channels in artificial channel is a challenging task.In this work,we demonstrate that a strategic application of steric code-based social self-sorting offers a novel means to enhance ion transport selectivities of artificial ion channels,alongside with boosted ion transport activities.More specifically,two types of mutually compatible sterically bulky groups(benzo-crown ether and tert-butyl group)were appended onto a monopeptide-based scaffold,which can order the bulky groups onto the same side of a one-dimensionally aligned H-bonded structure.Strong steric repulsions among the same type of bulky groups(either benzo-crown ethers or tert-butyl groups),which are forced into proximity by H-bonds,favor the formation of hetero-oligomeric ensem-bles that carry an alternative arrangement of sterically compatible benzo-crown ethers and tert-butyl groups,rather than homo-oligomeric ensembles containing a single type of either benzo-crown ethers or tert-butyl groups.Coupled with side chain tuning,this social self-sorting strategy delivers highly ac-tive hetero-oligomeric K+-selective ion channel(5F12-BF12)_(n),displaying the highest K+/Na+selectivity of 20.1 among artificial potassium channels and an excellent ECso value of 0.50μmol/L(0.62 mo1%relative to lipids)in terms of single channel concentration.展开更多
In analyses of protein families that may serve as drug targets,membrane-associated G-protein-coupled receptors(GPCRs)dominate,followed by ion channels,transporters,and—to a lesser extent—membrane-bound enzymes.Howev...In analyses of protein families that may serve as drug targets,membrane-associated G-protein-coupled receptors(GPCRs)dominate,followed by ion channels,transporters,and—to a lesser extent—membrane-bound enzymes.However,various challenges put such membrane proteins among key groups of underutilized opportunities for the application of therapeutic antibodies.Antibodies hold the promise of exquisite specificity,as they are able to target even specific conformations of a particular membrane protein,as well as adaptability through engineering into various antibody formats.However,the ease of raising and isolating specific,effective antibodies targeting membrane proteins depends on many factors.In particular,the generation of specific antibodies is easier when targeting larger,simpler,extracellular domains with greater uniqueness of amino acid sequence.The rareness of such ideal conditions is illustrated by the limited number of approved biologics for targeting GPCRs and other complex membrane proteins.Challenges in developing antibodies to complex membrane proteins such as GPCRs,ion channels,transporters,and membrane-bound enzymes can be addressed by the design of the antigen,antibody-generation strategies,lead optimization technologies,and antibody modalities.A better understanding of the membrane proteins being targeted would facilitate mechanism-based drug discovery.This review describes the advantages and challenges of targeting complex membrane proteins with antibodies and discusses the preparation of membrane protein antigens and antibody generation,illustrated by select examples of success.展开更多
We describe here a class of unconventional ion transporters,molecular rotors that transport ions through a rotating function rather than via traditional carrier or channel mechanisms.Mimicking macroscopic rotors,these...We describe here a class of unconventional ion transporters,molecular rotors that transport ions through a rotating function rather than via traditional carrier or channel mechanisms.Mimicking macroscopic rotors,these molecular rotors consist of three modularly tunable components,i.e.,a membrane-anchoring stator,a crown ether-containing rotator for ion binding and transport,and a triple bond-based axle that allows the rotator to freely rotate around the stator in the lipid membrane.Lipid bilayer experiments reveal the generally high ability of all molecular rotors in promoting the highly efficient transmembrane K^(+)flux(EC50 values=0.49-1.37 mol%relative to lipid).While molecular rotors differing only in the ion-binding unit exhibit similar ion transport activities,those differing in the rotator’s length display activity differences by up to 174%.展开更多
Membrane transport processes are indispensable for many aspects of plant physiology including mineral nutrition,solute storage,cell metabolism,cell signaling,osmoregulation,cell growth,and stress responses.Completion ...Membrane transport processes are indispensable for many aspects of plant physiology including mineral nutrition,solute storage,cell metabolism,cell signaling,osmoregulation,cell growth,and stress responses.Completion of genome sequencing in diverse plant species and the development of multiple genomic tools have marked a new era in understanding plant membrane transport at the mechanistic level.Genes coding for a galaxy of pumps,channels,and carriers that facilitate various membrane transport processes have been identified while multiple approaches are developed to dissect the physiological roles as well as to define the transport capacities of these transport systems.Furthermore,signaling networks dictating the membrane transport processes are established to fully understand the regulatory mechanisms.Here,we review recent research progress in the discovery and characterization of the components in plant membrane transport that take advantage of plant genomic resources and other experimental tools.We also provide our perspectives for future studies in the field.展开更多
The traditional approach to utilizing an ion-relay mechanism for ion transport requires three or more ion-relay stations.Herein,we describe a novel strategy,incorporating a swing action to realize a minimal ion-relay ...The traditional approach to utilizing an ion-relay mechanism for ion transport requires three or more ion-relay stations.Herein,we describe a novel strategy,incorporating a swing action to realize a minimal ion-relay mechanism via only two relay stations.This swing-relay mechanism was achieved using a class of crown ether-appended,long-armed molecular tetrahedrons(MTs).These MTs comprise ion-relaying crown units attached to a rigid tetrahedral core via flexible alkyl linkers,which act as the mobile arms and endow the crown units with great mobility to swing.展开更多
文摘Vascular plants contain two gene families that encode monosaccharide transporter proteins. The classical monosaccharide transporter（-like） gene superfamily is large and functionally diverse, while the recently identified SWEET transporter family is smaller and, thus far, only found to transport glucose. These transporters play essential roles at many levels, ranging from organelles to the whole plant. Many family members are essential for cellular homeostasis and reproductive success. Although most transporters do not directly participate in long-distance transport, their indirect roles greatly impact carbon allocation and transport flux to the heterotrophic tissues of the plant. Functional characterization of some members from both gene families has revealed their diverse roles in carbohydrate partitioning, phloem function, resource allocation, plant defense, and sugar signaling. This review highlights the broad impacts and implications of monosaccharide transport by describing some of the functional roles of the monosaccharide transporter（-like） superfamily and the SWEET transporter family.
基金funded by the Key-Area Research and Development Program of Guangdong Province(2020B020219004)the IndoAustralian Biotechnology Fund(BT/Indo-Aus/09/03/2015)provided by the Department of Biotechnology,Government of India+2 种基金the AISRF48490 Grant by the Department of Industry,Innovation and Science,Australiathe National Natural Science Foundation of China(31870249)the National Distinguished Expert Project(WQ20174400441)。
文摘Salinity is one of the major abiotic stresses which impose constraints to plant growth and production.Rice(Oryza sativa L.)is one of the most important staple food crops and a model monocot plant.Its production is expanding into regions that are affected by soil salinity,requiring cultivars more tolerant to saline conditions.Understanding the molecular mechanisms of such tolerance could lay a foundation for varietal improvement of salt tolerance in rice.In spite of extensive studies exploring the mechanism of salt tolerance,there has been limited progress in breeding for increased salinity tolerance.In this review,we summarize the information about the major molecular mechanisms underlying salinity tolerance in rice and further discuss the limitations in breeding for salinity tolerance.We show that numerous gene families and interaction networks are involved in the regulation of rice responses to salinity,prompting a need for a comprehensive functional analysis.We also show that most studies are based on whole-plant level analyses with only a few reports focused on tissue-and/or cell-specific gene expression.More details of salt-responsive channel and transporter activities at tissue-and cell-specific level still need to be documented before these traits can be incorporated into elite rice germplasm.Thus,future studies should focus on diversity of available genetic resources and,particular,wild rice relatives,to reincorporate salinity tolerance traits lost during domestication.
文摘Proplastids are undifferentiated plastids of meristematic tissues that synthesize amino acids for protein synthesis, fatty acids for membrane lipid production, and purines and pyrimidines for DNA and RNA synthesis. Unlike chloroplasts, proplastids depend on supply, with reducing power, energy, and precursor metabolites from the remainder of the cell. Comparing proplastid and chloroplast envelope proteomes and the corresponding transcriptomes of leaves and shoot apex revealed a clearly distinct composition of the proplastid envelope. It is geared towards import of metabolic precursors and export of product metabolites for the rapidly dividing cell. The analysis also suggested a new role for the triosephosphate translocator in meristematic tissues, identified the route of organic nitrogen import into proplastids, and detected an adenine nucleotide exporter. The protein import complex contains the import receptors Toc120 and Toc132 and lacks the redox sensing complex subunits of Tic32, Tic55, and Tic62, which mirrors the expression patterns of the corresponding genes in leaves and the shoot apex. We further show that the protein composition of the internal membrane system is similar to etioplasts, as it is dominated by the ATP synthase complex and thus remarkably differs from that of chloroplast thylakoids.
文摘Due to the presence of plastids, eukaryotic photosynthetic cells represent the most highly compartmentalized eukaryotic cells. This high degree of compartmentation requires the transport of solutes across intracellular membrane systems by specific membrane transporters. In this review, we summarize the recent progress on functionally characterized intracellular plant membrane transporters and we link transporter functions to Arabidopsis gene identifiers and to the transporter classification system. In addition, we outline challenges in further elucidating the plant membrane permeome and we provide an outline of novel approaches for the functional characterization of membrane transporters.
文摘Cholesterol is an essential component of the mammalian plasma membrane because it promotes membrane stability without comprising membrane fluidity. Given this important cellular role, cholesterol levels are tightly controlled at multiple levels. It has been clearly shown that cholesterol redistribution and depletion from the sperm membrane is a key part of the spermatozoon＇s preparation for fertilization. Some factors that regulate these events are described （e.g., bicarbonate, calcium） but the mechanisms underlying cholesterol export are poorly understood. How does a hydrophobic cholesterol molecule inserted in the sperm plasma membrane enter the energetically unfavorable aqueous surroundings？ This review will provide an overview of knowledge in this area and highlight our gaps in understanding. The overall aim is to better understand cholesterol redistribution in the sperm plasma membrane, its relation to the possible activation of a cholesterol transporter and the role of cholesterol acceptors. Armed with such knowledlze, sl）erm handlin~ techniques can be adapted to better prepare spermatozoa for in vitro and in vivo fertilization.
文摘The plant sucrose transporter SUT1 （from Solanum tuberosum, S. lycopersicum, or Zea mays） exhibits redoxdependent dimerization and targeting if heterologously expressed in S. cerevisiae （Krtigel et al., 2008）. It was also shown that SUT1 is present in motile vesicles when expressed in tobacco cells and that its targeting to the plasma membrane is reversible. StSUT1 is internalized in the presence of brefeldin A （BFA） in yeast, plant cells, and in mature sieve elements as confirmed by immunolocalization. These results were confirmed here and the dynamics of intracellular SUT1 localization were further elucidated. Inhibitor studies revealed that vesicle movement of SUT1 is actin-dependent. BFA-mediated effects might indicate that anterograde vesicle movement is possible even in mature sieve elements, and could involve components of the cytoskeleton that were previously thought to be absent in SEs. Our results are in contradiction to this old dogma of plant physiology and the potential of mature sieve elements should therefore be re-evaluated. In addition, SUT1 internalization was found to be dependent on the plasma membrane lipid composition. SUT1 belongs to the detergent-resistant membrane （DRM） fraction in planta and is targeted to membrane raft-like microdomains when expressed in yeast （Kr（igel et al,, 2008）, Here, SUT1-GFP expression in different yeast mutants, which were unable to perform en- docytosis and/or raft formation, revealed a strong link between SUT1 raft localization, the sterol composition and mem- brane potential of the yeast plasma membrane, and the capacity of the SUT1 protein to be internalized by endocytosis. The results provide new insight into the regulation of sucrose transport and the mechanism of endocytosis in plant cells.
基金foundations from Chinese Academy of Sciences and Special Funds for Major State Basic reseaxch of China (G1999053903).
文摘GABA transporter 1(GAT1) takes important roles in multiple physiological processes through the uptake and release of GABA, but the regulation of GAT1 gene expression in different tissues is rarely known. To address the question, first, 5’ Rapid amplification of cDNA end (RACE) was used to determine GAT1 transcriptional starting sites in neonatal mouse cerebral cortex and intestine, adult mouse brain and adult rat testis. The products of 5’RACE were confirmed by DNA sequencing. We found that the transcript of GAT1 in neonatal mouse cerebral cortex and adult mouse brain starts at the same site (inside of exon 1), while in mouse intestine, GAT1 starts transcription in intron 1, and in rat testis, the transcript of GAT1 has an additional untranslation exon to the 5’ direction.
文摘The Major Facilitator Superfamily(MFS)is ubiquitous in living organisms and represents the largest group of secondary active membrane transporters.In plants,significant research efforts have focused on the role of specific families within the MFS,particularly those transporting macronutrients(C,N,and P)that constitute the vast majority of the members of this superfamily.Other MFS families remain less explored,although a plethora of additional substrates and physiological functions have been uncovered.Nevertheless,the lack of a systematic approach to analyzing the MFS as a whole has obscured the high diversity and versatility of these transporters.Here,we present a phylogenetic analysis of all annotated MFS domaincontaining proteins encoded in the Arab/dops/s fA?a//ana genome and propose that this superfamily of transporters consists of 218 members,clustered in 22 families.In reviewing the available information regarding the diversity in biological functions and substrates of Arab/dops/s MFS members,we provide arguments for intensified research on these membrane transporters to unveil the breadth of their physiological relevance,disclose the molecular mechanisms underlying their mode of action,and explore their biotechnological potential.
基金supported by the National Natural Science Foundation of China(No.22271049)Fuzhou University,Xiamen University and Northwestern Polytechnical University.
文摘Replicating extraordinarily high membrane transport selectivity of protein channels in artificial channel is a challenging task.In this work,we demonstrate that a strategic application of steric code-based social self-sorting offers a novel means to enhance ion transport selectivities of artificial ion channels,alongside with boosted ion transport activities.More specifically,two types of mutually compatible sterically bulky groups(benzo-crown ether and tert-butyl group)were appended onto a monopeptide-based scaffold,which can order the bulky groups onto the same side of a one-dimensionally aligned H-bonded structure.Strong steric repulsions among the same type of bulky groups(either benzo-crown ethers or tert-butyl groups),which are forced into proximity by H-bonds,favor the formation of hetero-oligomeric ensem-bles that carry an alternative arrangement of sterically compatible benzo-crown ethers and tert-butyl groups,rather than homo-oligomeric ensembles containing a single type of either benzo-crown ethers or tert-butyl groups.Coupled with side chain tuning,this social self-sorting strategy delivers highly ac-tive hetero-oligomeric K+-selective ion channel(5F12-BF12)_(n),displaying the highest K+/Na+selectivity of 20.1 among artificial potassium channels and an excellent ECso value of 0.50μmol/L(0.62 mo1%relative to lipids)in terms of single channel concentration.
基金This work was partly supported by the Cancer Prevention and Research Institute of Texas,USA(PR150551 and RP190561)the Welch Foundation(AU-0042-20030616)+1 种基金The work was also supported by the National Natural Science Foundation of China(31700778 and 31320103918)Jiangsu Province’s Key Laboratory of Medicine(XK201135).
文摘In analyses of protein families that may serve as drug targets,membrane-associated G-protein-coupled receptors(GPCRs)dominate,followed by ion channels,transporters,and—to a lesser extent—membrane-bound enzymes.However,various challenges put such membrane proteins among key groups of underutilized opportunities for the application of therapeutic antibodies.Antibodies hold the promise of exquisite specificity,as they are able to target even specific conformations of a particular membrane protein,as well as adaptability through engineering into various antibody formats.However,the ease of raising and isolating specific,effective antibodies targeting membrane proteins depends on many factors.In particular,the generation of specific antibodies is easier when targeting larger,simpler,extracellular domains with greater uniqueness of amino acid sequence.The rareness of such ideal conditions is illustrated by the limited number of approved biologics for targeting GPCRs and other complex membrane proteins.Challenges in developing antibodies to complex membrane proteins such as GPCRs,ion channels,transporters,and membrane-bound enzymes can be addressed by the design of the antigen,antibody-generation strategies,lead optimization technologies,and antibody modalities.A better understanding of the membrane proteins being targeted would facilitate mechanism-based drug discovery.This review describes the advantages and challenges of targeting complex membrane proteins with antibodies and discusses the preparation of membrane protein antigens and antibody generation,illustrated by select examples of success.
基金This work was supported by Northwestern Poly-technical University.
文摘We describe here a class of unconventional ion transporters,molecular rotors that transport ions through a rotating function rather than via traditional carrier or channel mechanisms.Mimicking macroscopic rotors,these molecular rotors consist of three modularly tunable components,i.e.,a membrane-anchoring stator,a crown ether-containing rotator for ion binding and transport,and a triple bond-based axle that allows the rotator to freely rotate around the stator in the lipid membrane.Lipid bilayer experiments reveal the generally high ability of all molecular rotors in promoting the highly efficient transmembrane K^(+)flux(EC50 values=0.49-1.37 mol%relative to lipid).While molecular rotors differing only in the ion-binding unit exhibit similar ion transport activities,those differing in the rotator’s length display activity differences by up to 174%.
基金This work is supported by the National Science Foundation(MCB-1714795)Innovative Genomics Institute at University of CaliforniaBerkeley to S.L.,and the National Natural Science Foundation(grant no.31770266)to F.-G.Z.C.W.is sponsored in part by Tang Distinguished Scholarship at University of California-Berkeley.
文摘Membrane transport processes are indispensable for many aspects of plant physiology including mineral nutrition,solute storage,cell metabolism,cell signaling,osmoregulation,cell growth,and stress responses.Completion of genome sequencing in diverse plant species and the development of multiple genomic tools have marked a new era in understanding plant membrane transport at the mechanistic level.Genes coding for a galaxy of pumps,channels,and carriers that facilitate various membrane transport processes have been identified while multiple approaches are developed to dissect the physiological roles as well as to define the transport capacities of these transport systems.Furthermore,signaling networks dictating the membrane transport processes are established to fully understand the regulatory mechanisms.Here,we review recent research progress in the discovery and characterization of the components in plant membrane transport that take advantage of plant genomic resources and other experimental tools.We also provide our perspectives for future studies in the field.
基金Northwestern Polytechnical University and the NanoBio Lab(Biomedical Research Council,Agency for Science,Technology,and Research).
文摘The traditional approach to utilizing an ion-relay mechanism for ion transport requires three or more ion-relay stations.Herein,we describe a novel strategy,incorporating a swing action to realize a minimal ion-relay mechanism via only two relay stations.This swing-relay mechanism was achieved using a class of crown ether-appended,long-armed molecular tetrahedrons(MTs).These MTs comprise ion-relaying crown units attached to a rigid tetrahedral core via flexible alkyl linkers,which act as the mobile arms and endow the crown units with great mobility to swing.
