Structure of the enabled VASP homology 1 domain-peptide complex: A key component in the spatial control of actin assembly

The Enabled/VASP homology 1 (EVH1;also called WH1) domain is an interaction module found in several proteins implicated in actin-based cell motility. EVH1 domains bind the consensus proline-rich motif FPPPP and are required f or targeting the actin assembly machinery to sites of cytoskeletal remodeli ng. The crystal structure of the mammalian Enabled (Mena) EVH1 domain compl exed with a peptide ligand reveals a mechanism of recognition distinct from that used by other proline-binding modules. The EVH1 domain fold is unexpe ctedly similar to that of the pleckstrin homology domain, a membrane locali zation module. This finding demonstrates the functional plasticity of the p leckstrin homology fold as a binding scaffold and suggests that membrane as sociation may play an auxiliary role in EVH1 targeting.