As we know more about Zika virus(ZIKV), as well as its linkage to birth defects(microcephaly) and autoimmune neurological syndromes, we realize the importance of developing an efficient vaccine against it. Zika virus ...As we know more about Zika virus(ZIKV), as well as its linkage to birth defects(microcephaly) and autoimmune neurological syndromes, we realize the importance of developing an efficient vaccine against it. Zika virus disease has affected many countries and is becoming a major public health concern. To deal with the infection of ZIKV, plenty of experiments have been done on selection of neutralizing antibodies that can target the envelope(E) protein on the surface of the virion. However, the existence of antibody-dependent enhancement(ADE) effect might limit the use of them as therapeutic candidates. In this review, we classify the neutralizing antibodies against ZIKV based on the epitopes and summarize the resolved structural information on antibody/antigen complex from X-ray crystallography and cryo-electron microscopy(cryo-EM), which might be useful for further development of potent neutralizing antibodies and vaccines toward clinical use.展开更多
The human Shwachman-Diamond syndrome （SDS） is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly...The human Shwachman-Diamond syndrome （SDS） is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly factor, elongation factor l-like （Eft1）, to pro- mote the release of eukaryotic initiation factor 6 （elF6） from the late-stage cytoplasmic 60S precursors. In the present work, we characterized, both biochemically and structurally, the interaction between the 60S subunit and SBDS protein （Sdolp） from yeast. Our data show that Sdolp interacts tightly with the mature 60S subunit in vitro through its domain I and II, and is capable of bridging two 60S subunits to form a stable 2：2 dimer. Structural analysis indicates that Sdolp bind to the ribosomal P-site, in the proximity of uL16 and uL5, and with direct contact to H69 and H38. The dynamic nature of Sdolp on the 60S subunit, together with its strategic binding position, suggests a surveillance role of Sdolp in monitoring the conformational maturation of the ribosomal P-site. Altogether, our data support a con- formational signal-relay cascade during late-stage 60S maturation, involving uL16, Sdolp, and Efllp, which interrogates the functional P-site to control the departure of the anti-association factor elF6.展开更多
Recent technical breakthroughs in cryo-electron microscopy（cryo-EM） revolutionized structural biology, which led to the 2017 Nobel Prize in chemistry being awarded to three scientists, Jacques Dubochet, Joachim Fran...Recent technical breakthroughs in cryo-electron microscopy（cryo-EM） revolutionized structural biology, which led to the 2017 Nobel Prize in chemistry being awarded to three scientists, Jacques Dubochet, Joachim Frank, and Richard Henderson, who made groundbreaking contributions to the development of cryo-EM. In this review, I will give a comprehensive review of the developmental history of cryo-EM, the technical aspects of the breakthrough in cryo-EM leading to the structural biology revolution, including electron microscopy, image recording devices and image processing algorithms,and the major scientific achievements by Chinese researchers employing cryo-EM, covering protein complexes involved in or related to gene expression and regulation, protein synthesis and degradation, membrane proteins, immunity, and viruses.Finally, I will give a perspective outlook on the development of cryo-EM in the future.展开更多
基金funded by the External Cooperation Program of Chinese Academy of Sciences (Grant No. 153211KYSB20160001)the National Key Research and Development Program of China (Grant No. 2016YFC1202902)+1 种基金the Key Program of Chinese Academy of Sciences (Grant No. ZDRW-ZS2016-4)funded by FNLCR Contract HHSN261200800001E
文摘As we know more about Zika virus(ZIKV), as well as its linkage to birth defects(microcephaly) and autoimmune neurological syndromes, we realize the importance of developing an efficient vaccine against it. Zika virus disease has affected many countries and is becoming a major public health concern. To deal with the infection of ZIKV, plenty of experiments have been done on selection of neutralizing antibodies that can target the envelope(E) protein on the surface of the virion. However, the existence of antibody-dependent enhancement(ADE) effect might limit the use of them as therapeutic candidates. In this review, we classify the neutralizing antibodies against ZIKV based on the epitopes and summarize the resolved structural information on antibody/antigen complex from X-ray crystallography and cryo-electron microscopy(cryo-EM), which might be useful for further development of potent neutralizing antibodies and vaccines toward clinical use.
文摘The human Shwachman-Diamond syndrome （SDS） is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly factor, elongation factor l-like （Eft1）, to pro- mote the release of eukaryotic initiation factor 6 （elF6） from the late-stage cytoplasmic 60S precursors. In the present work, we characterized, both biochemically and structurally, the interaction between the 60S subunit and SBDS protein （Sdolp） from yeast. Our data show that Sdolp interacts tightly with the mature 60S subunit in vitro through its domain I and II, and is capable of bridging two 60S subunits to form a stable 2：2 dimer. Structural analysis indicates that Sdolp bind to the ribosomal P-site, in the proximity of uL16 and uL5, and with direct contact to H69 and H38. The dynamic nature of Sdolp on the 60S subunit, together with its strategic binding position, suggests a surveillance role of Sdolp in monitoring the conformational maturation of the ribosomal P-site. Altogether, our data support a con- formational signal-relay cascade during late-stage 60S maturation, involving uL16, Sdolp, and Efllp, which interrogates the functional P-site to control the departure of the anti-association factor elF6.
基金Project supported by the National Key Research and Development Program of China(Grant No.2017YFA0504700)the National Natural Science Foundation of China(Grant Nos.31570732 and 31770785)
文摘Recent technical breakthroughs in cryo-electron microscopy（cryo-EM） revolutionized structural biology, which led to the 2017 Nobel Prize in chemistry being awarded to three scientists, Jacques Dubochet, Joachim Frank, and Richard Henderson, who made groundbreaking contributions to the development of cryo-EM. In this review, I will give a comprehensive review of the developmental history of cryo-EM, the technical aspects of the breakthrough in cryo-EM leading to the structural biology revolution, including electron microscopy, image recording devices and image processing algorithms,and the major scientific achievements by Chinese researchers employing cryo-EM, covering protein complexes involved in or related to gene expression and regulation, protein synthesis and degradation, membrane proteins, immunity, and viruses.Finally, I will give a perspective outlook on the development of cryo-EM in the future.
