2A3Z

Ternary complex of the WH2 domain of WASP with Actin-DNAse I

2A3Z の概要

• エントリーDOI: 10.2210/pdb2a3z/pdb
• 関連するPDBエントリー: 2A40 2A41 2A42
• 分子名称: Actin, alpha skeletal muscle, Deoxyribonuclease-1, Wiskott-Aldrich syndrome protein, ... (10 entities in total)
• 機能のキーワード: wasp, wh2, actin, dnase i, arp2/3, structural protein
• 由来する生物種: Oryctolagus cuniculus (rabbit); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 75345.95

構造登録者

Chereau, D.,Kerff, F.,Dominguez, R. (登録日: 2005-06-27, 公開日: 2005-11-01, 最終更新日: 2023-08-23)

主引用文献

Chereau, D.,Kerff, F.,Graceffa, P.,Grabarek, Z.,Langsetmo, K.,Dominguez, R.
Actin-bound structures of Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 and the implications for filament assembly
Proc.Natl.Acad.Sci.Usa, 102:16644-16649, 2005

PubMed Abstract: Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 (WH2) is a small and widespread actin-binding motif. In the WASP family, WH2 plays a role in filament nucleation by Arp2/3 complex. Here we describe the crystal structures of complexes of actin with the WH2 domains of WASP, WASP-family verprolin homologous protein, and WASP-interacting protein. Despite low sequence identity, WH2 shares structural similarity with the N-terminal portion of the actin monomer-sequestering thymosin beta domain (Tbeta). We show that both domains inhibit nucleotide exchange by targeting the cleft between actin subdomains 1 and 3, a common binding site for many unrelated actin-binding proteins. Importantly, WH2 is significantly shorter than Tbeta but binds actin with approximately 10-fold higher affinity. WH2 lacks a C-terminal extension that in Tbeta4 becomes involved in monomer sequestration by interfering with intersubunit contacts in F-actin. Owing to their shorter length, WH2 domains connected in tandem by short linkers can coexist with intersubunit contacts in F-actin and are proposed to function in filament nucleation by lining up actin subunits along a filament strand. The WH2-central region of WASP-family proteins is proposed to function in an analogous way by forming a special class of tandem repeats whose function is to line up actin and Arp2 during Arp2/3 nucleation. The structures also suggest a mechanism for how profilin-binding Pro-rich sequences positioned N-terminal to WH2 could feed actin monomers directly to WH2, thereby playing a role in filament elongation.

PubMed: 16275905
DOI: 10.1073/pnas.0507021102

実験手法

X-RAY DIFFRACTION (2.078 Å)