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4u0a

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Revision as of 13:55, 10 May 2019

Hexameric HIV-1 CA in complex with CPSF6 peptide, P6 crystal form

Structural highlights

4u0a is a 2 chain structure with sequence from Hiv-1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	gag (HIV-1)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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). [CPSF6_HUMAN] Component of the cleavage factor Im complex (CFIm) that plays a key role in pre-mRNA 3'-processing. Involved in association with NUDT21/CPSF5 in pre-MRNA 3'-end poly(A) site cleavage and poly(A) addition. CPSF6 binds to cleavage and polyadenylation RNA substrates and promotes RNA looping.^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

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

References

↑ Ruegsegger U, Blank D, Keller W. Human pre-mRNA cleavage factor Im is related to spliceosomal SR proteins and can be reconstituted in vitro from recombinant subunits. Mol Cell. 1998 Jan;1(2):243-53. PMID:9659921
↑ Ruegsegger U, Beyer K, Keller W. Purification and characterization of human cleavage factor Im involved in the 3' end processing of messenger RNA precursors. J Biol Chem. 1996 Mar 15;271(11):6107-13. PMID:8626397
↑ Brown KM, Gilmartin GM. A mechanism for the regulation of pre-mRNA 3' processing by human cleavage factor Im. Mol Cell. 2003 Dec;12(6):1467-76. PMID:14690600
↑ Kim S, Yamamoto J, Chen Y, Aida M, Wada T, Handa H, Yamaguchi Y. Evidence that cleavage factor Im is a heterotetrameric protein complex controlling alternative polyadenylation. Genes Cells. 2010 Sep 1;15(9):1003-13. doi: 10.1111/j.1365-2443.2010.01436.x., Epub 2010 Jul 29. PMID:20695905 doi:10.1111/j.1365-2443.2010.01436.x
↑ Yang Q, Coseno M, Gilmartin GM, Doublie S. Crystal Structure of a Human Cleavage Factor CFI(m)25/CFI(m)68/RNA Complex Provides an Insight into Poly(A) Site Recognition and RNA Looping. Structure. 2011 Feb 2. PMID:21295486 doi:10.1016/j.str.2010.12.021
↑ 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/4u0a"

@@ Line 1: / Line 1: @@
 ==Hexameric HIV-1 CA in complex with CPSF6 peptide, P6 crystal form==
-<StructureSection load='4u0a' size='340' side='right' caption='[[4u0a]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
+<StructureSection load='4u0a' size='340' side='right'caption='[[4u0a]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4u0a]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U0A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U0A FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4u0a]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hiv-1 Hiv-1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4U0A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4U0A FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gag ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11698 HIV-1])</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=4u0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4u0a OCA], [http://pdbe.org/4u0a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4u0a RCSB], [http://www.ebi.ac.uk/pdbsum/4u0a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4u0a ProSAT]</span></td></tr>
 </table>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Hiv-1]]
+[[Category: Large Structures]]
 [[Category: Jacques, D A]]
 [[Category: James, L C]]

4u0a

From Proteopedia

Revision as of 13:55, 10 May 2019

Hexameric HIV-1 CA in complex with CPSF6 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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