6B72

A novel HIV-1 Nef dimer interface induced by a single octyl-glucoside molecule

6B72 の概要

• エントリーDOI: 10.2210/pdb6b72/pdb
• 分子名称: Protein Nef, octyl beta-D-glucopyranoside (2 entities in total)
• 機能のキーワード: hiv-1 nef, dimer, viral protein
• 由来する生物種: Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 107461.48

構造登録者

Wu, M.,Augelli-Szafran, C.E.,Ptak, R.G.,Smithgall, T.E. (登録日: 2017-10-03, 公開日: 2018-02-21, 最終更新日: 2024-03-13)

主引用文献

Wu, M.,Alvarado, J.J.,Augelli-Szafran, C.E.,Ptak, R.G.,Smithgall, T.E.
A single beta-octyl glucoside molecule induces HIV-1 Nef dimer formation in the absence of partner protein binding.
PLoS ONE, 13:e0192512-e0192512, 2018

PubMed Abstract: 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.

PubMed: 29415006
DOI: 10.1371/journal.pone.0192512

実験手法

X-RAY DIFFRACTION (3.2 Å)