Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan defects.However,the mechanistic link of cilia to CMD complications is still poorly understood.Her...Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan defects.However,the mechanistic link of cilia to CMD complications is still poorly understood.Herein,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols.Moreover,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl groups.Mechanistic studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium disassembly.In vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm flagella.These findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.展开更多
By the reaction of different aromatic dicarboxylic acid with zinc nitrate, three metal-carboxylate frameworks, [Zn3（BDC）3（EtOH）2]（1）, [Zn3（BDC）3（py）2]·2DMF（2）, and [Zn3（NH2-BDC）3（H2O）2]·5DMF...By the reaction of different aromatic dicarboxylic acid with zinc nitrate, three metal-carboxylate frameworks, [Zn3（BDC）3（EtOH）2]（1）, [Zn3（BDC）3（py）2]·2DMF（2）, and [Zn3（NH2-BDC）3（H2O）2]·5DMF（3） which are constructed on the same linear trinuclear Zn3（RCOO）6 secondary building units, have been synthesized and characterized by X-ray diffraction analyses. Structural analyses showed that there are terephthalic acids as ligand linkers to form the hxl topological layer structures for 1 and 2. The introduction of the rigid aromatic ring pyridine in 2 as the terminal co-ligand of Zn3-SBU to instead of the flexible ethanol in 1, will form the layer-pillared supramolecular systems with 2-D crisscross channels, through its π-π stacking interactions. Owing to the steric hindrance of amino groups, 3 was assembled into a three-dimensional porous structure with pcu topology derived from the 2-amino-terephthalic acid as linkers to connect the Zn3-SBUs through a head-to-tail type.展开更多
Understanding uranium-protein interaction is important for revealing the mechanism of uranyl ion(UO2+2)toxicity. In this study, we investigated the interaction between UO2+2and a quadruple mutant of cytochrome b5(E44/...Understanding uranium-protein interaction is important for revealing the mechanism of uranyl ion(UO2+2)toxicity. In this study, we investigated the interaction between UO2+2and a quadruple mutant of cytochrome b5(E44/48/56A/D60 A cyt b5, namely 4A cyt b5) by spectroscopic approaches. The four mutated negativelycharged surface residues of cyt b5 have been considered to be the interactive sites with cytochrome c(cyt c).Also, we studied the interaction between UO2+2and the protein-protein complex of 4A cyt b5-cyt c. The results were compared to the interaction between UO2+2and cyt b5, and the interaction between cyt c and cyt b5-cyt c complex, from previous studies. It was found that the interaction of UO2+2-cyt b5, i.e., uranyl ion binding to cyt b5 surface at Glu37 and Glu43 as previously proposed by molecular modeling, is regulated by both surface mutations of cyt b5 and its interacting protein partner cyt c. These provide valuable information on metal-protein-protein interactions and clues for understanding the mechanism of uranyl toxicity.展开更多
基金supported by grants from the National Natural Science Foundation of China(31991193 and 32230025)the National Key R&D Program of China(2021YFA1101001).
文摘Carbohydrate metabolism disorders(CMDs),such as diabetes,galactosemia,and mannosidosis,cause ciliopathy-like multiorgan defects.However,the mechanistic link of cilia to CMD complications is still poorly understood.Herein,we describe significant cilium disassembly upon treatment of cells with pathologically relevant aldoses rather than the corresponding sugar alcohols.Moreover,environmental aldehydes are able to trigger cilium disassembly by the steric hindrance effect of their formyl groups.Mechanistic studies reveal that aldehydes stimulate extracellular calcium influx across the plasma membrane,which subsequently activates the calmodulin-Aurora A-histone deacetylase 6 pathway to deacetylate axonemal microtubules and triggers cilium disassembly.In vivo experiments further show that Hdac6 knockout mice are resistant to aldehyde-induced disassembly of tracheal cilia and sperm flagella.These findings reveal a previously unrecognized role for formyl group-mediated cilium disassembly in the complications of CMDs.
基金supported by the National Natural Science Foundation of China(No.11375082,11305086,11175080)Science Foundation of Hunan Province Department of Education(No.12A117)the Project Sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry(Wang X.F.)
文摘By the reaction of different aromatic dicarboxylic acid with zinc nitrate, three metal-carboxylate frameworks, [Zn3（BDC）3（EtOH）2]（1）, [Zn3（BDC）3（py）2]·2DMF（2）, and [Zn3（NH2-BDC）3（H2O）2]·5DMF（3） which are constructed on the same linear trinuclear Zn3（RCOO）6 secondary building units, have been synthesized and characterized by X-ray diffraction analyses. Structural analyses showed that there are terephthalic acids as ligand linkers to form the hxl topological layer structures for 1 and 2. The introduction of the rigid aromatic ring pyridine in 2 as the terminal co-ligand of Zn3-SBU to instead of the flexible ethanol in 1, will form the layer-pillared supramolecular systems with 2-D crisscross channels, through its π-π stacking interactions. Owing to the steric hindrance of amino groups, 3 was assembled into a three-dimensional porous structure with pcu topology derived from the 2-amino-terephthalic acid as linkers to connect the Zn3-SBUs through a head-to-tail type.
基金Supported by National Natural Science Foundation of China(Nos.21101091 and 11275090)
文摘Understanding uranium-protein interaction is important for revealing the mechanism of uranyl ion(UO2+2)toxicity. In this study, we investigated the interaction between UO2+2and a quadruple mutant of cytochrome b5(E44/48/56A/D60 A cyt b5, namely 4A cyt b5) by spectroscopic approaches. The four mutated negativelycharged surface residues of cyt b5 have been considered to be the interactive sites with cytochrome c(cyt c).Also, we studied the interaction between UO2+2and the protein-protein complex of 4A cyt b5-cyt c. The results were compared to the interaction between UO2+2and cyt b5, and the interaction between cyt c and cyt b5-cyt c complex, from previous studies. It was found that the interaction of UO2+2-cyt b5, i.e., uranyl ion binding to cyt b5 surface at Glu37 and Glu43 as previously proposed by molecular modeling, is regulated by both surface mutations of cyt b5 and its interacting protein partner cyt c. These provide valuable information on metal-protein-protein interactions and clues for understanding the mechanism of uranyl toxicity.
