5l93
From Proteopedia
An atomic model of HIV-1 CA-SP1 reveals structures regulating assembly and maturation
Structural highlights
FunctionGAG_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 PubMedImmature HIV-1 assembles at, and buds from, the plasma membrane before proteolytic cleavage of the viral Gag polyprotein induces structural maturation. Maturation is blocked by protease and maturation inhibitors (MIs), abolishing infectivity. The CA (capsid) and SP1 (spacer peptide 1) region of Gag is the key regulator of assembly and maturation, and the target of MIs. Here we applied optimized cryo-electron tomography and subtomogram averaging to resolve this region within assembled immature HIV-1 particles at 3.9 A resolution and built an atomic model. The structure reveals a network of intra- and inter-molecular interactions mediating immature HIV-1 assembly. The proteolytic cleavage site between CA and SP1 is inaccessible to protease. We suggest that MIs prevent CA-SP1 cleavage by stabilizing the structure, and MI resistance develops by destabilizing CA-SP1. An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation.,Schur FK, Obr M, Hagen WJ, Wan W, Jakobi AJ, Kirkpatrick JM, Sachse C, Krausslich HG, Briggs JA Science. 2016 Jul 14. pii: aaf9620. PMID:27417497[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Large Structures | Arjen JJ | Briggs JAG | Hagen WJH | Kirkpatrick JM | Kraeusslich H-G | Obr M | Sachse C | Schur FKM | Wan W