2A42

Actin-DNAse I Complex

Summary for 2A42

• Entry DOI: 10.2210/pdb2a42/pdb
• Related: 2A3Z 2A40 2A41
• Descriptor: Actin, alpha skeletal muscle, Deoxyribonuclease-1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: actin, dnase i, structural protein
• Biological source: Oryctolagus cuniculus (rabbit); More
• Cellular location: Cytoplasm, cytoskeleton: P68135; Secreted: P00639
• Total number of polymer chains: 2
• Total formula weight: 72280.53

Authors

Chereau, D.,Kerff, F.,Dominguez, R. (deposition date: 2005-06-27, release date: 2005-11-01, Last modification date: 2023-08-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.85 Å)