3DS1

HIV-1 capsid C-terminal domain mutant (E187A) in complex with an inhibitor of particle assembly (CAI)

Summary for 3DS1

• Entry DOI: 10.2210/pdb3ds1/pdb
• Related: 3DPH 3DS0 3DS2 3DS3 3DS4 3DS5 3DTJ
• Descriptor: HIV-1 CAPSID PROTEIN, Peptide Inhibitor of capsid assembly (3 entities in total)
• Functional Keywords: hiv, capsid, mutant, inhibitor, assembly, polyprotein, complex (viral protein-peptide), mainly alpha, viral protein
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 2
• Total formula weight: 10918.45

Authors

Vaney, M.-C.,Igonet, S.,Rey, F.A. (deposition date: 2008-07-11, release date: 2008-09-02, Last modification date: 2023-08-30)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.6 Å)