5y9f - Revision history

OCA at 09:13, 21 October 2020

OCA — Wed, 21 Oct 2020 09:13:37 GMT

←Older revision		Revision as of 09:13, 21 October 2020
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	==Crystal structure of HPV59 pentamer in complex with the Fab fragment of antibody 28F10==		==Crystal structure of HPV59 pentamer in complex with the Fab fragment of antibody 28F10==
-	<StructureSection load='5y9f' size='340' side='right' caption='[[5y9f]], [[Resolution\|resolution]] 3.35Å' scene=''>	+	<StructureSection load='5y9f' size='340' side='right'caption='[[5y9f]], [[Resolution\|resolution]] 3.35Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5y9f]] is a 30 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y9F OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5Y9F FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5y9f]] is a 30 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y9F OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5Y9F 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=5y9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y9f OCA], [http://pdbe.org/5y9f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y9f RCSB], [http://www.ebi.ac.uk/pdbsum/5y9f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y9f ProSAT]</span></td></tr>	+	</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=5y9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y9f OCA], [http://pdbe.org/5y9f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y9f RCSB], [http://www.ebi.ac.uk/pdbsum/5y9f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y9f ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 17:		Line 17:
	</div>		</div>
	<div class="pdbe-citations 5y9f" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5y9f" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Antibody 3D structures\|Antibody 3D structures]]
		+	*[[Major capsid protein L1\|Major capsid protein L1]]
		+	*[[3D structures of non-human antibody\|3D structures of non-human antibody]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Li, S W]]		[[Category: Li, S W]]

OCA at 06:58, 25 October 2017

OCA — Wed, 25 Oct 2017 06:58:40 GMT

←Older revision		Revision as of 06:58, 25 October 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5y9f is ~~ON HOLD~~	+	==Crystal structure of HPV59 pentamer in complex with the Fab fragment of antibody 28F10==
		+	<StructureSection load='5y9f' size='340' side='right' caption='[[5y9f]], [[Resolution\|resolution]] 3.35Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5y9f]] is a 30 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5Y9F OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5Y9F 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=5y9f FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5y9f OCA], [http://pdbe.org/5y9f PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5y9f RCSB], [http://www.ebi.ac.uk/pdbsum/5y9f PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5y9f ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/Q81971_HPV59 Q81971_HPV59]] Forms an icosahedral capsid with a T=7 symmetry and a 50 nm diameter. The capsid is composed of 72 pentamers linked to each other by disulfide bonds and associated with L2 proteins. Binds to heparan sulfate proteoglycans on cell surface of basal layer keratinocytes to provide initial virion attachment. This binding mediates a conformational change in the virus capsid that facilitates efficient infection. The virion enters the host cell via endocytosis. During virus trafficking, L1 protein dissociates from the viral DNA and the genomic DNA is released to the host nucleus. The virion assembly takes place within the cell nucleus. Encapsulates the genomic DNA together with protein L2.[RuleBase:RU361248][SAAS:SAAS00505820]
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Persistent, high-risk human papillomavirus (HPV) infection is the primary cause of cervical cancer. Neutralizing antibodies elicited by L1-only virus-like particles (VLPs) can block HPV infection; however, the lack of high-resolution structures has limited our understanding of the mode of virus infection and the requirement for type specificity at the molecular level. Here, we describe two antibodies, A12A3 and 28F10, that specifically bind to and neutralize HPV58 and HPV59, respectively, through two distinct binding stoichiometries. We show that the epitopes of A12A3 are clustered in the DE loops of two adjacent HPV58 L1 monomers, whereas 28F10 recognizes the HPV59 FG loop of a single monomer. Via structure-based mutagenesis and analysis of antibody binding, we further identified the residues HPV58 D154, S168, and N170 and HPV59 M267, Q270, E273, Y276, K278, and R283, which play critical roles in virus infection. By substituting these strategic epitope residues into other HPV genotypes, we could then redirect the type-specific binding of the antibodies to these genotypes, thus highlighting the importance of these specific residues, HPV58 R161, S168, and N308 and HPV59 Q270, E273, and D281. Overall, our findings provide molecular insights into potential structural determinants of HPV required for infectivity and type specificity.IMPORTANCE High-risk human papillomaviruses (HPVs) are considered the major causative pathogens of cancers that affect epithelial mucosa, such as cervical cancer. However, because of the lack of high-resolution structural information on the sites of neutralization, we have yet to determine the precise mode of HPV infection and how different types of HPV cause infection. Our crystal structures in this study have uncovered discrete binding stoichiometries for two different antibodies. We show that one A12A3 Fab binds to the center of one HPV58 pentamer, whereas five 28F10 Fabs bind along the top fringe of one HPV59 pentamer. Furthermore, through targeted epitope analysis, we show that 6 to 7 discontinuous residues of the L1 major capsid protein of HPV are determinants, at least in part, for virus infection and type specificity. This knowledge will help us to unravel the process of HPV infection and can potentially be used to drive the development of therapeutics that target neutralization-sensitive sites.

-	~~Authors:~~ Li, S~~.W.~~, Li, Z.H.	+	Crystal Structures of Two Immune Complexes Identify Determinants for Viral Infectivity and Type-Specific Neutralization of Human Papillomavirus.,Li Z, Wang D, Gu Y, Song S, He M, Shi J, Liu X, Wei S, Li J, Yu H, Zheng Q, Yan X, Baker TS, Zhang J, McLellan JS, Li S, Xia N MBio. 2017 Sep 26;8(5). pii: e00787-17. doi: 10.1128/mBio.00787-17. PMID:28951471<ref>PMID:28951471</ref>

-	~~Description: Crystal structure~~ of ~~HPV59 pentamer in complex with~~ the ~~Fab fragment~~ of ~~antibody 28F10~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Li, ~~Z.H~~]]	+	<div class="pdbe-citations 5y9f" style="background-color:#fffaf0;"></div>
-	[[Category: Li, ~~S.W~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Mus musculus]]
		+	[[Category: Li, S W]]
		+	[[Category: Li, Z H]]
		+	[[Category: Capsid protein]]
		+	[[Category: Immune complex]]
		+	[[Category: Structural protein]]
		+	[[Category: Viral protein-immune system complex]]

OCA: Protected "5y9f" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 16:17:47 GMT

Protected "5y9f" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:17, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5y9f is ON HOLD Authors: Li, S.W., Li, Z.H. Description: Crystal structure of HPV59 pentamer in complex with the Fab fragment of antibody 28F10 [[C...

OCA — Wed, 27 Sep 2017 16:17:46 GMT

New page: '''Unreleased structure''' The entry 5y9f is ON HOLD Authors: Li, S.W., Li, Z.H. Description: Crystal structure of HPV59 pentamer in complex with the Fab fragment of antibody 28F10 [[C...

New page

'''Unreleased structure'''

The entry 5y9f is ON HOLD

Authors: Li, S.W., Li, Z.H.

Description: Crystal structure of HPV59 pentamer in complex with the Fab fragment of antibody 28F10
[[Category: Unreleased Structures]]
[[Category: Li, Z.H]]
[[Category: Li, S.W]]