1M4J

CRYSTAL STRUCTURE OF THE N-TERMINAL ADF-H DOMAIN OF MOUSE TWINFILIN ISOFORM-1

Summary for 1M4J

• Entry DOI: 10.2210/pdb1m4j/pdb
• Related: 1CFY 1COF 1EQY
• Descriptor: A6 gene product (2 entities in total)
• Functional Keywords: mixed beta-sheet, pair of alpha-helices, structural protein
• Biological source: Mus musculus (house mouse)
• Cellular location: Cytoplasm: Q91YR1
• Total number of polymer chains: 2
• Total formula weight: 32588.72

Authors

Paavilainen, V.O.,Merckel, M.C.,Falck, S.,Ojala, P.J.,Pohl, E.,Wilmanns, M.,Lappalainen, P. (deposition date: 2002-07-03, release date: 2002-11-13, Last modification date: 2024-02-14)

Primary citation

Paavilainen, V.O.,Merckel, M.C.,Falck, S.,Ojala, P.J.,Pohl, E.,Wilmanns, M.,Lappalainen, P.
Structural Conservation Between the Actin Monomer-binding Sites of Twinfilin and Actin-depolymerizing Factor (ADF)/Cofilin
J.Biol.Chem., 277:43089-43095, 2002

PubMed Abstract: Twinfilin is an evolutionarily conserved actin monomer-binding protein that regulates cytoskeletal dynamics in organisms from yeast to mammals. It is composed of two actin-depolymerization factor homology (ADF-H) domains that show approximately 20% sequence identity to ADF/cofilin proteins. In contrast to ADF/cofilins, which bind both G-actin and F-actin and promote filament depolymerization, twinfilin interacts only with G-actin. To elucidate the molecular mechanisms of twinfilin-actin monomer interaction, we determined the crystal structure of the N-terminal ADF-H domain of twinfilin and mapped its actin-binding site by site-directed mutagenesis. This domain has similar overall structure to ADF/cofilins, and the regions important for actin monomer binding in ADF/cofilins are especially well conserved in twinfilin. Mutagenesis studies show that the N-terminal ADF-H domain of twinfilin and ADF/cofilins also interact with actin monomers through similar interfaces, although the binding surface is slightly extended in twinfilin. In contrast, the regions important for actin-filament interactions in ADF/cofilins are structurally different in twinfilin. This explains the differences in actin-interactions (monomer versus filament binding) between twinfilin and ADF/cofilins. Taken together, our data show that the ADF-H domain is a structurally conserved actin-binding motif and that relatively small structural differences at the actin interfaces of this domain are responsible for the functional variation between the different classes of ADF-H domain proteins.

PubMed: 12207032
DOI: 10.1074/jbc.M208225200

Experimental method

X-RAY DIFFRACTION (1.6 Å)