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Title: X-ray crystal structures of native HIV-1 capsid protein reveal conformational variability

The detailed molecular interactions between native HIV-1 capsid protein (CA) hexamers that shield the viral genome and proteins have been elusive. In this paper, 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. Finally, inherent structural plasticity, hydration layer rearrangement, and effector binding affect capsid stability and have functional implications for the retroviral life cycle.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [6]
  1. Univ. of Missouri, Columbia, MO (United States). Christopher S. Bond Life Sciences Center. Dept. of Chemistry
  2. Univ. of Missouri, Columbia, MO (United States). Christopher S. Bond Life Sciences Center. School of Medicine. Dept. of Molecular Microbiology and Immunology
  3. National Cancer Inst., Frederick, MD (United States). Center for Cancer Research. Basic Research Lab.
  4. Univ. of Missouri, Columbia, MO (United States). Dept. of Chemistry. Dept. of Biochemistry
  5. Univ. of Virginia, Charlottesville, VA (United States). School of Medicine. Dept. of Molecular Physiology and Biological Physics
  6. Univ. of Missouri, Columbia, MO (United States). Christopher S. Bond Life Sciences Center. School of Medicine. Dept. of Molecular Microbiology and Immunology. Dept. of Biochemistry
Publication Date:
OSTI Identifier:
1214294
Grant/Contract Number:
AC02-05CH11231; AI112417; AI120860; GM103368; AI076119; AI099284; AI100890; GM066087
Type:
Accepted Manuscript
Journal Name:
Science
Additional Journal Information:
Journal Volume: 349; Journal Issue: 6243; Journal ID: ISSN 0036-8075
Publisher:
AAAS
Research Org:
Univ. of Missouri, Columbia, MO (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH) (United States)
Contributing Orgs:
National Cancer Inst., Frederick, MD (United States); Univ. of Virginia, Charlottesville, VA (United States)
Country of Publication:
United States
Language:
ENGLISH
Subject:
60 APPLIED LIFE SCIENCES