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5k6g

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Revision as of 09:22, 1 July 2020

Crystal structure of prefusion-stabilized RSV F single-chain 9-24 DS-Cav1 variant.

Structural highlights

5k6g is a 1 chain structure with sequence from Hrsva. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	5k6b, 5k6c, 5k6f, 5k6h, 5k6i
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

Structure-based design of vaccines, particularly the iterative optimization used so successfully in the structure-based design of drugs, has been a long-sought goal. We previously developed a first-generation vaccine antigen called DS-Cav1, comprising a prefusion-stabilized form of the fusion (F) glycoprotein, which elicits high-titer protective responses against respiratory syncytial virus (RSV) in mice and macaques. Here we report the improvement of DS-Cav1 through iterative cycles of structure-based design that significantly increased the titer of RSV-protective responses. The resultant second-generation 'DS2'-stabilized immunogens have their F subunits genetically linked, their fusion peptides deleted and their interprotomer movements stabilized by an additional disulfide bond. These DS2 immunogens are promising vaccine candidates with superior attributes, such as their lack of a requirement for furin cleavage and their increased antigenic stability against heat inactivation. The iterative structure-based improvement described here may have utility in the optimization of other vaccine antigens.

Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV.,Joyce MG, Zhang B, Ou L, Chen M, Chuang GY, Druz A, Kong WP, Lai YT, Rundlet EJ, Tsybovsky Y, Yang Y, Georgiev IS, Guttman M, Lees CR, Pancera M, Sastry M, Soto C, Stewart-Jones GB, Thomas PV, Van Galen JG, Baxa U, Lee KK, Mascola JR, Graham BS, Kwong PD Nat Struct Mol Biol. 2016 Aug 1. doi: 10.1038/nsmb.3267. PMID:27478931^[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
↑ Joyce MG, Zhang B, Ou L, Chen M, Chuang GY, Druz A, Kong WP, Lai YT, Rundlet EJ, Tsybovsky Y, Yang Y, Georgiev IS, Guttman M, Lees CR, Pancera M, Sastry M, Soto C, Stewart-Jones GB, Thomas PV, Van Galen JG, Baxa U, Lee KK, Mascola JR, Graham BS, Kwong PD. Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV. Nat Struct Mol Biol. 2016 Aug 1. doi: 10.1038/nsmb.3267. PMID:27478931 doi:http://dx.doi.org/10.1038/nsmb.3267

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/5k6g"

@@ Line 1: / Line 1: @@
 ==Crystal structure of prefusion-stabilized RSV F single-chain 9-24 DS-Cav1 variant.==
-<StructureSection load='5k6g' size='340' side='right' caption='[[5k6g]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
+<StructureSection load='5k6g' size='340' side='right'caption='[[5k6g]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5k6g]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K6G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K6G FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5k6g]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Hrsva Hrsva]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K6G OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5K6G FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5k6b|5k6b]], [[5k6c|5k6c]], [[5k6f|5k6f]], [[5k6h|5k6h]], [[5k6i|5k6i]]</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=5k6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k6g OCA], [http://pdbe.org/5k6g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k6g RCSB], [http://www.ebi.ac.uk/pdbsum/5k6g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k6g 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=5k6g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k6g OCA], [http://pdbe.org/5k6g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k6g RCSB], [http://www.ebi.ac.uk/pdbsum/5k6g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k6g ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Hrsva]]
+[[Category: Large Structures]]
 [[Category: Joyce, M G]]
 [[Category: Kwong, P D]]

5k6g

From Proteopedia

Revision as of 09:22, 1 July 2020

Crystal structure of prefusion-stabilized RSV F single-chain 9-24 DS-Cav1 variant.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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