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A single β-octyl glucoside molecule induces HIV-1 Nef dimer formation in the absence of partner protein binding

Journal Article · · PLoS ONE
 [1];  [2];  [1];  [3];  [2];  [4]
  1. Southern Research Institute, Birmingham, AL (United States)
  2. Univ. of Pittsburgh School of Medicine, Pittsburgh, PA (United States)
  3. Southern Research Institute, Frederick, MD (United States)
  4. Univ. of Washington, Seattle, WA (United States)
+ Show Author Affiliations
The HIV-1 Nef accessory protein is essential for viral pathogenicity and AIDS progression. Nef forms complexes with multiple host cell factors to facilitate viral replication and promote immune escape of HIV-infected cells. Previous X-ray crystal structures demonstrate that Nef forms homodimers, the orientation of which are influenced by host cell binding partners. In cell-based fluorescence complementation assays, Nef forms homodimers at the plasma membrane. However, recombinant Nef proteins often exist as monomers in solution, suggesting that membrane interaction may also trigger monomer to dimer transitions. In this study, we show that monomeric Nef core proteins can be induced to form dimers in the presence of low concentrations of the non-ionic surfactant, β-octyl glucoside (βOG). X-ray crystallography revealed that a single βOG molecule is present in the Nef dimer, with the 8-carbon acyl chain of the ligand binding to a hydrophobic pocket formed by the dimer interface. This Nef-βOG dimer interface involves helix αB, as observed in previous dimer structures, as well as a helix formed by N-terminal residues 54–66. Nef dimer formation is stabilized in solution by the addition of βOG, providing biochemical validation for the crystal structure. These observations together suggest that the interaction with host cell lipid mediators or other hydrophobic ligands may play a role in Nef dimerization, which has been previously linked to multiple Nef functions including host cell protein kinase activation, CD4 downregulation, and enhancement of HIV-1 replication.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
OSTI ID:
1420993
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 2 Vol. 13; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Antiretroviral Drugs Alter the Content of Extracellular Vesicles from HIV-1-Infected Cells journal May 2018
How HIV Nef Proteins Hijack Membrane Traffic To Promote Infection journal October 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
HIV-1
crystal structure
dimerization
dimers (chemical physics)
host cells
molecular structure
protein structure
viral replication