3DS2

HIV-1 capsid C-terminal domain mutant (Y169A)

3DS2 の概要

• エントリーDOI: 10.2210/pdb3ds2/pdb
• 関連するPDBエントリー: 3DPH 3DS0 3DS1 3DS3 3DS4 3DS5 3DTJ
• 分子名称: HIV-1 CAPSID PROTEIN (2 entities in total)
• 機能のキーワード: hiv, capsid, mutant, assembly, polyprotein, mainly alpha, viral protein
• 由来する生物種: Human immunodeficiency virus 1 (HIV-1)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18877.65

構造登録者

Vaney, M.-C.,Igonet, S.,Rey, F.A. (登録日: 2008-07-11, 公開日: 2008-09-02, 最終更新日: 2023-08-30)

主引用文献

Bartonova, V.,Igonet, S.,Sticht, J.,Glass, B.,Habermann, A.,Vaney, M.C.,Sehr, P.,Lewis, J.,Rey, F.A.,Krausslich, H.G.
Residues in the HIV-1 Capsid Assembly Inhibitor Binding Site Are Essential for Maintaining the Assembly-competent Quaternary Structure of the Capsid Protein.
J.Biol.Chem., 283:32024-32033, 2008

PubMed Abstract: Morphogenesis of infectious HIV-1 involves budding of immature virions followed by proteolytic disassembly of the Gag protein shell and subsequent assembly of processed capsid proteins (CA) into the mature HIV-1 core. The dimeric interface between C-terminal domains of CA (C-CA) has been shown to be important for both immature and mature assemblies. We previously reported a CA-binding peptide (CAI) that blocks both assembly steps in vitro. The three-dimensional structure of the C-CA/CAI complex revealed an allosteric effect of CAI that alters the C-CA dimer interface. Based on this structure, we now investigated the phenotypes of mutations in the binding pocket. CA variants carrying mutations Y169A, L211A, or L211S had a reduced affinity for CAI and were unable to form mature-like particles in vitro. These mutations also blocked morphological conversion to mature virions in tissue culture and abolished infectivity. X-ray crystallographic analyses of the variant C-CA domains revealed that these alterations induced the same allosteric change at the dimer interface observed in the C-CA/CAI complex. These results point to a role of key interactions between conserved amino acids in the CAI binding pocket of C-CA in maintaining the correct conformation necessary for mature core assembly.

PubMed: 18772135
DOI: 10.1074/jbc.M804230200

実験手法

X-RAY DIFFRACTION (1.2 Å)