LIG_WH1

Wiskott-Aldrich syndrome protein (WASP) and WASP-interacting protein (WIP) form a complex that has a pivotal function in integrating sigalling cascades that lead to acting polymerization. The WASP-binding domain (WBD) in WIP is known to bind to the WH1 (WASP homology 1) domain of WASP and N-WASP. The strong sequence conservation between the WH1 and the EVH1 domains, including the residues involved in coordinating EVH1 binding to FPPPP ligands, suggested that the WH1 domain may also bind a prolin-rich ligand. Indeed, the WBD in WIP consists of 26% proline residues and contains four proline sequence motifs, one of which is closely related to the WASP EVH1-binding motif. However it was found that WH1 and EVH1 domains bind distinct sequence motifs. The N-WASP WH1-binding motif of WIP is highly conserved also in the mammalian WIP homologs CR16 and WICH, two proteins interacting with N-WASP.