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Science. 2015 Jul 3;349(6243):99-103. doi: 10.1126/science.aaa5936. Epub 2015 Jun 4.

STRUCTURAL VIROLOGY. X-ray crystal structures of native HIV-1 capsid protein reveal conformational variability.

Author information

1
Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA. Department of Chemistry, University of Missouri, Columbia, MO 65211, USA.
2
Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA. Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65211, USA.
3
Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA.
4
Department of Chemistry, University of Missouri, Columbia, MO 65211, USA. Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA.
5
Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
6
Christopher S. Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA. Department of Molecular Microbiology and Immunology, University of Missouri School of Medicine, Columbia, MO 65211, USA. Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA. sarafianoss@missouri.edu.

Abstract

The detailed molecular interactions between native HIV-1 capsid protein (CA) hexamers that shield the viral genome and proteins have been elusive. We report crystal structures describing interactions between CA monomers related by sixfold symmetry within hexamers (intrahexamer) and threefold and twofold symmetry between neighboring hexamers (interhexamer). The structures describe how CA builds hexagonal lattices, the foundation of mature capsids. Lattice structure depends on an adaptable hydration layer modulating interactions among CA molecules. Disruption of this layer alters interhexamer interfaces, highlighting an inherent structural variability. A CA-targeting antiviral affects capsid stability by binding across CA molecules and subtly altering interhexamer interfaces remote to the ligand-binding site. Inherent structural plasticity, hydration layer rearrangement, and effector binding affect capsid stability and have functional implications for the retroviral life cycle.

PMID:
26044298
PMCID:
PMC4584149
DOI:
10.1126/science.aaa5936
[Indexed for MEDLINE]
Free PMC Article

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