3REB

HIV-1 Nef protein in complex with engineered Hck-SH3 domain

3REB の概要

• エントリーDOI: 10.2210/pdb3reb/pdb
• 関連するPDBエントリー: 3RBB 3REA
• 分子名称: Protein Nef, Tyrosine-protein kinase HCK (2 entities in total)
• 機能のキーワード: hiv-1 nef, sh3 domain binding, signaling, hck sh3 domain, protein binding
• 由来する生物種: HIV-1 M:B_ARV2/SF2 (HIV-1); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 58842.09

構造登録者

Schulte, A.,Blankenfeldt, W.,Geyer, M. (登録日: 2011-04-04, 公開日: 2011-06-01, 最終更新日: 2023-09-13)

主引用文献

Breuer, S.,Schievink, S.I.,Schulte, A.,Blankenfeldt, W.,Fackler, O.T.,Geyer, M.
Molecular design, functional characterization and structural basis of a protein inhibitor against the HIV-1 pathogenicity factor Nef.
PLoS ONE, 6:e20033-e20033, 2011

PubMed Abstract: Increased spread of HIV-1 and rapid emergence of drug resistance warrants development of novel antiviral strategies. Nef, a critical viral pathogenicity factor that interacts with host cell factors but lacks enzymatic activity, is not targeted by current antiviral measures. Here we inhibit Nef function by simultaneously blocking several highly conserved protein interaction surfaces. This strategy, referred to as "wrapping Nef", is based on structure-function analyses that led to the identification of four target sites: (i) SH3 domain interaction, (ii) interference with protein transport processes, (iii) CD4 binding and (iv) targeting to lipid membranes. Screening combinations of Nef-interacting domains, we developed a series of small Nef interacting proteins (NIs) composed of an SH3 domain optimized for binding to Nef, fused to a sequence motif of the CD4 cytoplasmic tail and combined with a prenylation signal for membrane association. NIs bind to Nef in the low nM affinity range, associate with Nef in human cells and specifically interfere with key biological activities of Nef. Structure determination of the Nef-inhibitor complex reveals the molecular basis for binding specificity. These results establish Nef-NI interfaces as promising leads for the development of potent Nef inhibitors.

PubMed: 21625496
DOI: 10.1371/journal.pone.0020033

実験手法

X-RAY DIFFRACTION (3.45 Å)