This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

5kou

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 16:29, 11 December 2019

Crystal structure of the human astrovirus 2 capsid protein spike domain at 1.87-A resolution

Structural highlights

5kou is a 4 chain structure with sequence from H-ast2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	ORF2 (H-Ast2)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CAPSD_HASV2] The capsid polyprotein VP90 self-assembles and undergoes a proteolytic cleavage by host caspases to yield the VP70 virions. This immature virion is composed of 180 VP70 subunits with 90 dimeric spikes and displays a T=3 icosahedral symmetry. The mature virion is obtained by further cleavages resulting in three structural proteins VP25, VP27 and VP34. This forms contains only 30 spikes located on the icosahedral 2-fold axes. Plays a role in the attachment to target host cell. This attachment induces virion internalization through clathrin-dependent endocytosis (By similarity).

Publication Abstract from PubMed

Human astroviruses (HAstVs) are a leading cause of viral diarrhea in young children, the immune compromised, and the elderly. There are no vaccines or antiviral therapies against HAstV disease. Several lines of evidence point to the presence of protective antibodies in healthy adults as a mechanism governing protection against reinfection by HAstV. However, development of anti-HAstV therapies is hampered by the gap in knowledge of protective antibody epitopes on the HAstV capsid surface. Here, we report the structure of the HAstV capsid spike domain bound to the neutralizing monoclonal antibody PL-2. The antibody uses all six complementarity determining regions to bind to a quaternary epitope on each side of the dimeric capsid spike. We provide evidence that the HAstV capsid spike is a receptor binding domain and that the antibody neutralizes HAstV by blocking virus attachment to cells. We identify patches of conserved amino acids that overlap with the antibody epitope and may comprise a receptor-binding site. Our studies provide a foundation for the development of therapies to prevent and treat HAstV diarrheal disease. IMPORTANCE: Human astroviruses (HAstVs) infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. Despite the prevalence of this virus, little is known about how antibodies in healthy adults protect them against reinfection. Here, we determined the crystal structure of a complex of the HAstV capsid protein and a virus-neutralizing antibody. We show that the antibody binds to the outermost spike domain of the capsid, and we provide evidence that the antibody blocks virus attachment to human cells. Importantly, our findings suggest that a subunit-based vaccine focusing the immune system on the HAstV capsid spike domain could be effective in protecting children against HAstV disease.

Structure of a Human Astrovirus Capsid - Antibody Complex and Mechanistic Insights into Virus Neutralization.,Bogdanoff WA, Campos J, Perez EI, Yin L, Alexander DL, DuBois RM J Virol. 2016 Nov 2. pii: JVI.01859-16. PMID:27807234^[1]

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

References

↑ Bogdanoff WA, Campos J, Perez EI, Yin L, Alexander DL, DuBois RM. Structure of a Human Astrovirus Capsid - Antibody Complex and Mechanistic Insights into Virus Neutralization. J Virol. 2016 Nov 2. pii: JVI.01859-16. PMID:27807234 doi:http://dx.doi.org/10.1128/JVI.01859-16

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/5kou"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human astrovirus 2 capsid protein spike domain at 1.87-A resolution==
-<StructureSection load='5kou' size='340' side='right' caption='[[5kou]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
+<StructureSection load='5kou' size='340' side='right'caption='[[5kou]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5kou]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KOU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KOU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5kou]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/H-ast2 H-ast2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5KOU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5KOU 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=5kou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kou OCA], [http://pdbe.org/5kou PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kou RCSB], [http://www.ebi.ac.uk/pdbsum/5kou PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kou ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ORF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=12701 H-Ast2])</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=5kou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kou OCA], [http://pdbe.org/5kou PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5kou RCSB], [http://www.ebi.ac.uk/pdbsum/5kou PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5kou ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: H-ast2]]
+[[Category: Large Structures]]
 [[Category: Bogdanoff, W A]]
 [[Category: DuBois, R M]]

5kou

From Proteopedia

Revision as of 16:29, 11 December 2019

Crystal structure of the human astrovirus 2 capsid protein spike domain at 1.87-A resolution

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox