6apd
From Proteopedia
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(New page: '''Unreleased structure''' The entry 6apd is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures) |
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- | '''Unreleased structure''' | ||
- | + | ==Crystal structure of RSV F bound by AM22 and the infant antibody ADI-19425== | |
+ | <StructureSection load='6apd' size='340' side='right'caption='[[6apd]], [[Resolution|resolution]] 4.10Å' scene=''> | ||
+ | == Structural highlights == | ||
+ | <table><tr><td colspan='2'>[[6apd]] is a 15 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Respiratory_syncytial_virus Respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6APD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6APD FirstGlance]. <br> | ||
+ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.1Å</td></tr> | ||
+ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6apd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6apd OCA], [https://pdbe.org/6apd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6apd RCSB], [https://www.ebi.ac.uk/pdbsum/6apd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6apd ProSAT]</span></td></tr> | ||
+ | </table> | ||
+ | == Function == | ||
+ | [https://www.uniprot.org/uniprot/WAC_BPT4 WAC_BPT4] Chaperone responsible for attachment of long tail fibers to virus particle. Forms the fibrous structure on the neck of the virion called whiskers. During phage assembly, 6 fibritin molecules attach to each virion neck through their N-terminal domains, to form a collar with six fibers ('whiskers').[https://www.uniprot.org/uniprot/FUS_HRSVA FUS_HRSVA] Class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and plasma cell membrane fusion, the heptad repeat (HR) regions assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and plasma cell membranes. Directs fusion of viral and cellular membranes leading to delivery of the nucleocapsid into the cytoplasm. This fusion is pH independent and occurs directly at the outer cell membrane. The trimer of F1-F2 (protein F) interacts with glycoprotein G at the virion surface. Upon binding of G to heparan sulfate, the hydrophobic fusion peptide is unmasked and interacts with the cellular membrane, inducing the fusion between host cell and virion membranes. Notably, RSV fusion protein is able to interact directly with heparan sulfate and therefore actively participates in virus attachment. Furthermore, the F2 subunit was identifed as the major determinant of RSV host cell specificity. Later in infection, proteins F expressed at the plasma membrane of infected cells mediate fusion with adjacent cells to form syncytia, a cytopathic effect that could lead to tissue necrosis. The fusion protein is also able to trigger p53-dependent apoptosis.<ref>PMID:12663767</ref> <ref>PMID:18216092</ref> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | Respiratory syncytial virus (RSV) is a leading cause of infant mortality, and there are currently no licensed vaccines to protect this vulnerable population. A comprehensive understanding of infant antibody responses to natural RSV infection would facilitate vaccine development. Here, we isolated more than 450 RSV fusion glycoprotein (F)-specific antibodies from 7 RSV-infected infants and found that half of the antibodies recognized only two antigenic sites. Antibodies targeting both sites showed convergent sequence features, and structural studies revealed the molecular basis for their recognition of RSV F. A subset of antibodies targeting one of these sites displayed potent neutralizing activity despite lacking somatic mutations, and similar antibodies were detected in RSV-naive B cell repertoires, suggesting that expansion of these B cells in infants may be possible with suitably designed vaccine antigens. Collectively, our results provide fundamental insights into infant antibody responses and a framework for the rational design of age-specific RSV vaccines. | ||
- | + | Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation.,Goodwin E, Gilman MSA, Wrapp D, Chen M, Ngwuta JO, Moin SM, Bai P, Sivasubramanian A, Connor RI, Wright PF, Graham BS, McLellan JS, Walker LM Immunity. 2018 Feb 20;48(2):339-349.e5. doi: 10.1016/j.immuni.2018.01.005. Epub, 2018 Feb 3. PMID:29396163<ref>PMID:29396163</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | [[Category: | + | </div> |
+ | <div class="pdbe-citations 6apd" style="background-color:#fffaf0;"></div> | ||
+ | |||
+ | ==See Also== | ||
+ | *[[Antibody 3D structures|Antibody 3D structures]] | ||
+ | == References == | ||
+ | <references/> | ||
+ | __TOC__ | ||
+ | </StructureSection> | ||
+ | [[Category: Homo sapiens]] | ||
+ | [[Category: Human immunodeficiency virus 1]] | ||
+ | [[Category: Large Structures]] | ||
+ | [[Category: Respiratory syncytial virus]] | ||
+ | [[Category: McLellan JS]] | ||
+ | [[Category: Wrapp D]] |
Current revision
Crystal structure of RSV F bound by AM22 and the infant antibody ADI-19425
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