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5w23

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Revision as of 08:47, 30 September 2020

Crystal Structure of RSV F in complex with 5C4 Fab

Structural highlights

5w23 is a 9 chain structure with sequence from Hrsva and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
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

A licensed vaccine for respiratory syncytial virus (RSV) is unavailable, and passive prophylaxis with the antibody palivizumab is restricted to high-risk infants. Recently isolated antibodies 5C4 and D25 are substantially more potent than palivizumab, and a derivative of D25 is in clinical trials. Here we show that unlike D25, 5C4 preferentially neutralizes subtype A viruses. The crystal structure of 5C4 bound to the RSV fusion (F) protein reveals that the overall binding mode of 5C4 is similar to that of D25, but their angles of approach are substantially different. Mutagenesis and virological studies demonstrate that RSV F residue 201 is largely responsible for the subtype specificity of 5C4. These results improve our understanding of subtype-specific immunity and the neutralization breadth requirements of next-generation antibodies, and thereby contribute to the design of broadly protective RSV vaccines.

Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein.,Tian D, Battles MB, Moin SM, Chen M, Modjarrad K, Kumar A, Kanekiyo M, Graepel KW, Taher NM, Hotard AL, Moore ML, Zhao M, Zheng ZZ, Xia NS, McLellan JS, Graham BS Nat Commun. 2017 Nov 30;8(1):1877. doi: 10.1038/s41467-017-01858-w. PMID:29187732^[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
↑ Tian D, Battles MB, Moin SM, Chen M, Modjarrad K, Kumar A, Kanekiyo M, Graepel KW, Taher NM, Hotard AL, Moore ML, Zhao M, Zheng ZZ, Xia NS, McLellan JS, Graham BS. Structural basis of respiratory syncytial virus subtype-dependent neutralization by an antibody targeting the fusion glycoprotein. Nat Commun. 2017 Nov 30;8(1):1877. doi: 10.1038/s41467-017-01858-w. PMID:29187732 doi:http://dx.doi.org/10.1038/s41467-017-01858-w

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/5w23"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of RSV F in complex with 5C4 Fab==
-<StructureSection load='5w23' size='340' side='right' caption='[[5w23]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
+<StructureSection load='5w23' size='340' side='right'caption='[[5w23]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5w23]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Hrsva Hrsva] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W23 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W23 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5w23]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Hrsva Hrsva] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W23 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5W23 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5w23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w23 OCA], [http://pdbe.org/5w23 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w23 RCSB], [http://www.ebi.ac.uk/pdbsum/5w23 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w23 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5w23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w23 OCA], [http://pdbe.org/5w23 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w23 RCSB], [http://www.ebi.ac.uk/pdbsum/5w23 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w23 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 23: / Line 23: @@
 </StructureSection>
 [[Category: Hrsva]]
+[[Category: Large Structures]]
 [[Category: Lk3 transgenic mice]]
 [[Category: Battles, M B]]

5w23

From Proteopedia

Revision as of 08:47, 30 September 2020

Crystal Structure of RSV F in complex with 5C4 Fab

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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