4u0c

From Proteopedia

(Difference between revisions)

Revision as of 19:37, 25 December 2014

Hexameric HIV-1 CA in complex with Nup153 peptide, P6 crystal form

Structural highlights

4u0c is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	4u0a, 4u0b
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[GAG_HV1N5] Matrix protein p17 targets Gag and Gag-Pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex. Implicated in the release from host cell mediated by Vpu. Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex. Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers. p6-gag plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1 (By similarity). [NU153_HUMAN] Possible DNA-binding subunit of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane.

Publication Abstract from PubMed

The HIV-1 capsid is involved in all infectious steps from reverse transcription to integration site selection, and is the target of multiple host cell and pharmacologic ligands. However, structural studies have been limited to capsid monomers (CA), and the mechanistic basis for how these ligands influence infection is not well understood. Here we show that a multi-subunit interface formed exclusively within CA hexamers mediates binding to linear epitopes within cellular cofactors NUP153 and CPSF6, and is competed for by the antiretroviral compounds PF74 and BI-2. Each ligand is anchored via a shared phenylalanine-glycine (FG) motif to a pocket within the N-terminal domain of one monomer, and all but BI-2 also make essential interactions across the N-terminal domain: C-terminal domain (NTD:CTD) interface to a second monomer. Dissociation of hexamer into CA monomers prevents high affinity interaction with CPSF6 and PF74, and abolishes binding to NUP153. The second interface is conformationally dynamic, but binding of NUP153 or CPSF6 peptides is accommodated by only one conformation. NUP153 and CPSF6 have overlapping binding sites, but each makes unique CA interactions that, when mutated selectively, perturb cofactor dependency. These results reveal that multiple ligands share an overlapping interface in HIV-1 capsid that is lost upon viral disassembly.

Host Cofactors and Pharmacologic Ligands Share an Essential Interface in HIV-1 Capsid That Is Lost upon Disassembly.,Price AJ, Jacques DA, McEwan WA, Fletcher AJ, Essig S, Chin JW, Halambage UD, Aiken C, James LC PLoS Pathog. 2014 Oct 30;10(10):e1004459. doi: 10.1371/journal.ppat.1004459., eCollection 2014 Oct. PMID:25356722^[1]

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

References

↑ Price AJ, Jacques DA, McEwan WA, Fletcher AJ, Essig S, Chin JW, Halambage UD, Aiken C, James LC. Host Cofactors and Pharmacologic Ligands Share an Essential Interface in HIV-1 Capsid That Is Lost upon Disassembly. PLoS Pathog. 2014 Oct 30;10(10):e1004459. doi: 10.1371/journal.ppat.1004459., eCollection 2014 Oct. PMID:25356722 doi:http://dx.doi.org/10.1371/journal.ppat.1004459

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/4u0c"

@@ Line 6: / Line 6: @@
 <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=4u0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u0c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4u0c RCSB], [http://www.ebi.ac.uk/pdbsum/4u0c PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/GAG_HV1N5 GAG_HV1N5]] Matrix protein p17 targets Gag and Gag-Pol polyproteins to the plasma membrane via a multipartite membrane binding signal, that includes its myristoylated N-terminus. Also mediates nuclear localization of the preintegration complex. Implicated in the release from host cell mediated by Vpu.  Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex.  Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers.  p6-gag plays a role in budding of the assembled particle by interacting with the host class E VPS proteins TSG101 and PDCD6IP/AIP1 (By similarity). [[http://www.uniprot.org/uniprot/NU153_HUMAN NU153_HUMAN]] Possible DNA-binding subunit of the nuclear pore complex (NPC). The repeat-containing domain may be involved in anchoring components of the pore complex to the pore membrane.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4u0c

From Proteopedia

Revision as of 19:37, 25 December 2014

Hexameric HIV-1 CA in complex with Nup153 peptide, P6 crystal form

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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