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3rki

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Revision as of 19:15, 4 August 2016

Structural basis for immunization with post-fusion RSV F to elicit high neutralizing antibody titers

Structural highlights

3rki is a 3 chain structure with sequence from Hrsv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	F (HRSV)
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), the main cause of infant bronchiolitis, remains a major unmet vaccine need despite more than 40 years of vaccine research. Vaccine candidates based on a chief RSV neutralization antigen, the fusion (F) glycoprotein, have foundered due to problems with stability, purity, reproducibility, and potency. Crystal structures of related parainfluenza F glycoproteins have revealed a large conformational change between the prefusion and postfusion states, suggesting that postfusion F antigens might not efficiently elicit neutralizing antibodies. We have generated a homogeneous, stable, and reproducible postfusion RSV F immunogen that elicits high titers of neutralizing antibodies in immunized animals. The 3.2-A X-ray crystal structure of this substantially complete RSV F reveals important differences from homology-based structural models. Specifically, the RSV F crystal structure demonstrates the exposure of key neutralizing antibody binding sites on the surface of the postfusion RSV F trimer. This unanticipated structural feature explains the engineered RSV F antigen's efficiency as an immunogen. This work illustrates how structural-based antigen design can guide the rational optimization of candidate vaccine antigens.

Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers.,Swanson KA, Settembre EC, Shaw CA, Dey AK, Rappuoli R, Mandl CW, Dormitzer PR, Carfi A Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9619-24. Epub 2011 May 17. PMID:21586636^[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
↑ Swanson KA, Settembre EC, Shaw CA, Dey AK, Rappuoli R, Mandl CW, Dormitzer PR, Carfi A. Structural basis for immunization with postfusion respiratory syncytial virus fusion F glycoprotein (RSV F) to elicit high neutralizing antibody titers. Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9619-24. Epub 2011 May 17. PMID:21586636 doi:10.1073/pnas.1106536108

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/3rki"

@@ Line 1: / Line 1: @@
 ==Structural basis for immunization with post-fusion RSV F to elicit high neutralizing antibody titers==
 <StructureSection load='3rki' size='340' side='right' caption='[[3rki]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3rki]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_respiratory_syncytial_virus Human respiratory syncytial virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RKI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RKI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3rki]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hrsv Hrsv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RKI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RKI FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11250 Human respiratory syncytial virus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11250 HRSV])</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=3rki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rki OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rki RCSB], [http://www.ebi.ac.uk/pdbsum/3rki PDBsum]</span></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=3rki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rki OCA], [http://pdbe.org/3rki PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3rki RCSB], [http://www.ebi.ac.uk/pdbsum/3rki PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3rki ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3rki" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human respiratory syncytial virus]]
+[[Category: Hrsv]]
 [[Category: Carfi, A]]
 [[Category: Dey, A K]]

3rki

From Proteopedia

Revision as of 19:15, 4 August 2016

Structural basis for immunization with post-fusion RSV F to elicit high neutralizing antibody titers

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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