3DAW

Structure of the actin-depolymerizing factor homology domain in complex with actin

Summary for 3DAW

• Entry DOI: 10.2210/pdb3daw/pdb
• Related: 2A42 2HD7
• Descriptor: Actin, alpha skeletal muscle, Twinfilin-1, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: actin depolymerisation, actin binding proteins, cytoskeleton, structural protein-contractile protein complex, structural protein-structural protein regulator complex, structural protein/structural protein regulator
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm, cytoskeleton: P68135; Cytoplasm: Q91YR1
• Total number of polymer chains: 2
• Total formula weight: 61995.19

Authors

Paavilainen, V.O.,Oksanen, E.,Goldman, A.,Lappalainen, P. (deposition date: 2008-05-30, release date: 2008-07-29, Last modification date: 2023-11-01)

Primary citation

Paavilainen, V.O.,Oksanen, E.,Goldman, A.,Lappalainen, P.
Structure of the actin-depolymerizing factor homology domain in complex with actin
J.Cell Biol., 182:51-59, 2008

PubMed Abstract: Actin dynamics provide the driving force for many cellular processes including motility and endocytosis. Among the central cytoskeletal regulators are actin-depolymerizing factor (ADF)/cofilin, which depolymerizes actin filaments, and twinfilin, which sequesters actin monomers and caps filament barbed ends. Both interact with actin through an ADF homology (ADF-H) domain, which is also found in several other actin-binding proteins. However, in the absence of an atomic structure for the ADF-H domain in complex with actin, the mechanism by which these proteins interact with actin has remained unknown. Here, we present the crystal structure of twinfilin's C-terminal ADF-H domain in complex with an actin monomer. This domain binds between actin subdomains 1 and 3 through an interface that is conserved among ADF-H domain proteins. Based on this structure, we suggest a mechanism by which ADF/cofilin and twinfilin inhibit nucleotide exchange of actin monomers and present a model for how ADF/cofilin induces filament depolymerization by weakening intrafilament interactions.

PubMed: 18625842
DOI: 10.1083/jcb.200803100

Experimental method

X-RAY DIFFRACTION (2.55 Å)