3DS3
HIV-1 capsid C-terminal domain mutant (Y169A) in complex with an inhibitor of particle assembly (CAI)
Summary for 3DS3
| Entry DOI | 10.2210/pdb3ds3/pdb |
| Related | 3DPH 3DS0 3DS1 3DS2 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 | 4 |
| Total formula weight | 21768.79 |
| Authors | Igonet, S.,Vaney, M.C.,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 Cited by 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: 18772135DOI: 10.1074/jbc.M804230200 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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