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5u68

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Revision as of 09:11, 1 January 2020

Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus

Structural highlights

5u68 is a 6 chain structure with sequence from Hrsva and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

Publication Abstract from PubMed

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are two closely related viruses that cause bronchiolitis and pneumonia in infants and the elderly1, with a significant health burden2-6. There are no licensed vaccines or small-molecule antiviral treatments specific to these two viruses at present. A humanized murine monoclonal antibody (palivizumab) is approved to treat high-risk infants for RSV infection7,8, but other treatments, as well as vaccines, for both viruses are still in development. Recent epidemiological modelling suggests that cross-immunity between RSV, HMPV and human parainfluenzaviruses may contribute to their periodic outbreaks9, suggesting that a deeper understanding of host immunity to these viruses may lead to enhanced strategies for their control. Cross-reactive neutralizing antibodies to the RSV and HMPV fusion (F) proteins have been identified10,11. Here, we examine the structural basis for cross-reactive antibody binding to RSV and HMPV F protein by two related, independently isolated antibodies, MPE8 and 25P13. We solved the structure of the MPE8 antibody bound to RSV F protein and identified the 25P13 antibody from an independent blood donor. Our results indicate that both antibodies use germline residues to interact with a conserved surface on F protein that could guide the emergence of cross-reactivity. The induction of similar cross-reactive neutralizing antibodies using structural vaccinology approaches could enhance intrinsic cross-immunity to these paramyxoviruses and approaches to controlling recurring outbreaks.

Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus.,Wen X, Mousa JJ, Bates JT, Lamb RA, Crowe JE Jr, Jardetzky TS Nat Microbiol. 2017 Jan 30;2:16272. doi: 10.1038/nmicrobiol.2016.272. PMID:28134915^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Schlender J, Zimmer G, Herrler G, Conzelmann KK. Respiratory syncytial virus (RSV) fusion protein subunit F2, not attachment protein G, determines the specificity of RSV infection. J Virol. 2003 Apr;77(8):4609-16. PMID:12663767
↑ Eckardt-Michel J, Lorek M, Baxmann D, Grunwald T, Keil GM, Zimmer G. The fusion protein of respiratory syncytial virus triggers p53-dependent apoptosis. J Virol. 2008 Apr;82(7):3236-49. Epub 2008 Jan 23. PMID:18216092 doi:JVI.01887-07
↑ Wen X, Mousa JJ, Bates JT, Lamb RA, Crowe JE Jr, Jardetzky TS. Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus. Nat Microbiol. 2017 Jan 30;2:16272. doi: 10.1038/nmicrobiol.2016.272. PMID:28134915 doi:http://dx.doi.org/10.1038/nmicrobiol.2016.272

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5u68"

@@ Line 1: / Line 1: @@
 ==Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus==
-<StructureSection load='5u68' size='340' side='right' caption='[[5u68]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
+<StructureSection load='5u68' size='340' side='right'caption='[[5u68]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5u68]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U68 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U68 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5u68]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Hrsva Hrsva] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U68 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U68 FirstGlance]. <br>
 </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5u68 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u68 OCA], [http://pdbe.org/5u68 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u68 RCSB], [http://www.ebi.ac.uk/pdbsum/5u68 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u68 ProSAT]</span></td></tr>
 </table>
@@ Line 21: / Line 21: @@
 __TOC__
 </StructureSection>
+[[Category: Hrsva]]
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Jardetzky, T S]]
 [[Category: Wen, X]]

5u68

From Proteopedia

Revision as of 09:11, 1 January 2020

Structural basis for antibody cross-neutralization of respiratory syncytial virus and human metapneumovirus

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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