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4wym

From Proteopedia

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Structural basis of HIV-1 capsid recognition by CPSF6

Structural highlights

4wym is a 23 chain structure with sequence from Homo sapiens and Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE). Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
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).

Publication Abstract from PubMed

Upon infection of susceptible cells by HIV-1, the conical capsid formed by approximately 250 hexamers and 12 pentamers of the CA protein is delivered to the cytoplasm. The capsid shields the RNA genome and proteins required for reverse transcription. In addition, the surface of the capsid mediates numerous host-virus interactions, which either promote infection or enable viral restriction by innate immune responses. In the intact capsid, there is an intermolecular interface between the N-terminal domain (NTD) of one subunit and the C-terminal domain (CTD) of the adjacent subunit within the same hexameric ring. The NTD-CTD interface is critical for capsid assembly, both as an architectural element of the CA hexamer and pentamer and as a mechanistic element for generating lattice curvature. Here we report biochemical experiments showing that PF-3450074 (PF74), a drug that inhibits HIV-1 infection, as well as host proteins cleavage and polyadenylation specific factor 6 (CPSF6) and nucleoporin 153 kDa (NUP153), bind to the CA hexamer with at least 10-fold higher affinities compared with nonassembled CA or isolated CA domains. The crystal structure of PF74 in complex with the CA hexamer reveals that PF74 binds in a preformed pocket encompassing the NTD-CTD interface, suggesting that the principal inhibitory target of PF74 is the assembled capsid. Likewise, CPSF6 binds in the same pocket. Given that the NTD-CTD interface is a specific molecular signature of assembled hexamers in the capsid, binding of NUP153 at this site suggests that key features of capsid architecture remain intact upon delivery of the preintegration complex to the nucleus.

Structural basis of HIV-1 capsid recognition by PF74 and CPSF6.,Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, Taylor AB, Demeler B, Pornillos O, Ganser-Pornillos BK, Diaz-Griffero F, Ivanov DN, Yeager M Proc Natl Acad Sci U S A. 2014 Dec 17. pii: 201419945. PMID:25518861^[1]

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

References

↑ Bhattacharya A, Alam SL, Fricke T, Zadrozny K, Sedzicki J, Taylor AB, Demeler B, Pornillos O, Ganser-Pornillos BK, Diaz-Griffero F, Ivanov DN, Yeager M. Structural basis of HIV-1 capsid recognition by PF74 and CPSF6. Proc Natl Acad Sci U S A. 2014 Dec 17. pii: 201419945. PMID:25518861 doi:http://dx.doi.org/10.1073/pnas.1419945112

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4wym"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4wym]] is a 23 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_type_1_(NEW_YORK-5_ISOLATE) Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WYM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WYM FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4wym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wym OCA], [https://pdbe.org/4wym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wym RCSB], [https://www.ebi.ac.uk/pdbsum/4wym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wym ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4wym FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wym OCA], [https://pdbe.org/4wym PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wym RCSB], [https://www.ebi.ac.uk/pdbsum/4wym PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wym ProSAT]</span></td></tr>
 </table>
 == Function ==

4wym

From Proteopedia

Current revision

Structural basis of HIV-1 capsid recognition by CPSF6

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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