6rwg
From Proteopedia
Structure of HIV-1 CAcSP1NC mutant(W41A,M42A) interacting with maturation inhibitor EP39
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 PubMedDuring the maturation of HIV-1 particle, the Gag polyprotein is cleaved into several proteins by the HIV-1 protease. These proteins rearrange to form infectious virus particles. In this study, the solution structure and dynamics of a monomeric mutated domain encompassing the C-terminal of capsid, the spacer peptide SP1 and the nucleocapsid from Gag was characterized by Nuclear Magnetic Resonance in the presence of maturation inhibitor EP39, a more hydro-soluble derivative of BVM. We show that the binding of EP39 decreases the dynamics of CA-SP1 junction, especially the QVT motif in SP1, and perturbs the natural coil-helix equilibrium on both sides of the SP1 domain by stabilizing the transient alpha helical structure. Our results provide new insight into the structure and dynamics of the SP1 domain and how HIV-1 maturation inhibitors interfere with this domain. They offer additional clues for the development of new second generation inhibitors targeting HIV-1 maturation. The HIV-1 maturation inhibitor, EP39, interferes with the dynamic helix-coil equilibrium of the CA-SP1 junction of Gag.,Chen X, Coric P, Larue V, Turcaud S, Wang X, Nonin-Lecomte S, Bouaziz S Eur J Med Chem. 2020 Jul 18;204:112634. doi: 10.1016/j.ejmech.2020.112634. PMID:32717487[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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