View source for 6b43


==CryoEM structure and atomic model of the Kaposi's sarcoma-associated herpesvirus capsid==
<SX load='6b43' size='340' side='right' viewer='molstar' caption='[[6b43]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6b43]] is a 46 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_herpesvirus_8 Human herpesvirus 8]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3j9a 3j9a]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B43 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6B43 FirstGlance]. <br>
</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=6b43 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b43 OCA], [http://pdbe.org/6b43 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b43 RCSB], [http://www.ebi.ac.uk/pdbsum/6b43 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b43 ProSAT]</span></td></tr>
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== Function ==
[[http://www.uniprot.org/uniprot/C7E5A9_HHV8 C7E5A9_HHV8]] Structural component of the T=16 icosahedral capsid. The capsid is composed of pentamers and hexamers of major capsid protein/MCP, which are linked together by heterotrimers called triplexes. These triplexes are formed by a single molecule of triplex protein 1/TRX1 and two copies of triplex protein 2/TRX2. Additionally, TRX1 is required for efficient transport of TRX2 to the nucleus, which is the site of capsid assembly.[HAMAP-Rule:MF_04019] [[http://www.uniprot.org/uniprot/D0UZN7_HHV8 D0UZN7_HHV8]] Self-assembles to form an icosahedral capsid with a T=16 symmetry, about 200 nm in diameter, and consisting of 150 hexons and 12 pentons (total of 162 capsomers). Hexons form the edges and faces of the capsid and are each composed of six MCP molecules. In contrast, one penton is found at each of the 12 vertices. Eleven of the pentons are MCP pentamers, while the last vertex is occupied by the portal complex. The capsid is surrounded by a layer of proteinaceous material designated the tegument which, in turn, is enclosed in an envelope of host cell-derived lipids containing virus-encoded glycoproteins.[HAMAP-Rule:MF_04016] [[http://www.uniprot.org/uniprot/Q76RF6_HHV8 Q76RF6_HHV8]] Structural component of the T=16 icosahedral capsid. The capsid is composed of pentamers and hexamers of major capsid protein/MCP, which are linked together by heterotrimers called triplexes. These triplexes are formed by a single molecule of triplex protein 1/TRX1 and two copies of triplex protein 2/TRX2. Additionally, TRX1 is required for efficient transport of TRX2 to the nucleus, which is the site of capsid assembly.[HAMAP-Rule:MF_04018] [[http://www.uniprot.org/uniprot/Q76RF4_HHV8 Q76RF4_HHV8]] Participates in the assembly of the infectious particles by decorating the outer surface of the capsid shell and thus forming a layer between the capsid and the tegument. Complexes composed of the major capsid protein and small capsomere-interacting protein/SCP assemble together in the host cytoplasm and are translocated to the nucleus, where they accumulate and participate in capsid assembly.[HAMAP-Rule:MF_04022] 
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== Publication Abstract from PubMed ==
Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, a cancer that commonly affects patients with AIDS and which is endemic in sub-Saharan Africa. The KSHV capsid is highly pressurized by its double-stranded DNA genome, as are the capsids of the eight other human herpesviruses. Capsid assembly and genome packaging of herpesviruses are prone to interruption and can therefore be targeted for the structure-guided development of antiviral agents. However, herpesvirus capsids-comprising nearly 3,000 proteins and over 1,300 A in diameter-present a formidable challenge to atomic structure determination and functional mapping of molecular interactions. Here we report a 4.2 A resolution structure of the KSHV capsid, determined by electron-counting cryo-electron microscopy, and its atomic model, which contains 46 unique conformers of the major capsid protein (MCP), the smallest capsid protein (SCP) and the triplex proteins Tri1 and Tri2. Our structure and mutagenesis results reveal a groove in the upper domain of the MCP that contains hydrophobic residues that interact with the SCP, which in turn crosslinks with neighbouring MCPs in the same hexon to stabilize the capsid. Multiple levels of MCP-MCP interaction-including six sets of stacked hairpins lining the hexon channel, disulfide bonds across channel and buttress domains in neighbouring MCPs, and an interaction network forged by the N-lasso domain and secured by the dimerization domain-define a robust capsid that is resistant to the pressure exerted by the enclosed genome. The triplexes, each composed of two Tri2 molecules and a Tri1 molecule, anchor to the capsid floor via a Tri1 N-anchor to plug holes in the MCP network and rivet the capsid floor. These essential roles of the MCP N-lasso and Tri1 N-anchor are verified by serial-truncation mutageneses. Our proof-of-concept demonstration of the use of polypeptides that mimic the smallest capsid protein to inhibit KSHV lytic replication highlights the potential for exploiting the interaction hotspots revealed in our atomic structure to develop antiviral agents.

Structure and mutagenesis reveal essential capsid protein interactions for KSHV replication.,Dai X, Gong D, Lim H, Jih J, Wu TT, Sun R, Zhou ZH Nature. 2018 Jan 25;553(7689):521-525. doi: 10.1038/nature25438. Epub 2018 Jan, 17. PMID:29342139<ref>PMID:29342139</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Molstar|Molstar]]
== References ==
<references/>
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[[Category: Human herpesvirus 8]]
[[Category: Large Structures]]
[[Category: Dai, X H]]
[[Category: Gong, D Y]]
[[Category: Sun, R]]
[[Category: Zhou, Z H]]
[[Category: Dsdna virus capsid assembly]]
[[Category: Hk97-like fold]]
[[Category: Human tumor virus]]
[[Category: Virus]]