3DS4: Hiv-1 Capsid C-terminal Domain Mutant (l211s) In Complex With An Inhibitor Of Particle Assembly (cai)

Citation:
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.
PDB ID: 3DS4Download
MMDB ID: 66501
PDB Deposition Date: 2008/7/11
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 1.12  Å
Source Organism:
Human immunodeficiency virus type 1 (NEW YORK-5 ISOLATE)
Similar Structures:
Biological Unit for 3DS4: trimeric; determined by author and by software (PISA)
Molecular Components in 3DS4
Label Count Molecule
Proteins (3 molecules)
2
Hiv-1 Capsid Protein
Molecule annotation
1
Peptide Inhibitor of Capsid Assembly
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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