Structure of the N-WASP EVH1 domain-WIP complex: insight into the molecular basis of Wiskott-Aldrich Syndrome. Cell 2002 Nov 15;111(4):565-76
Date
11/20/2002Pubmed ID
12437929DOI
10.1016/s0092-8674(02)01076-0Scopus ID
2-s2.0-0037112347 (requires institutional sign-in at Scopus site) 138 CitationsAbstract
Missense mutants that cause the immune disorder Wiskott-Aldrich Syndrome (WAS) map primarily to the Enabled/VASP homology 1 (EVH1) domain of the actin regulatory protein WASP. This domain has been implicated in both peptide and phospholipid binding. We show here that the N-WASP EVH1 domain does not bind phosphatidyl inositol-(4,5)-bisphosphate, as previously reported, but does specifically bind a 25 residue motif from the WASP Interacting Protein (WIP). The NMR structure of the complex reveals a novel recognition mechanism-the WIP ligand, which is far longer than canonical EVH1 ligands, wraps around the domain, contacting a narrow but extended surface. This recognition mechanism provides a basis for understanding the effects of mutations that cause WAS.
Author List
Volkman BF, Prehoda KE, Scott JA, Peterson FC, Lim WAAuthors
Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of WisconsinBrian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Carrier Proteins
Cytoskeletal Proteins
Ligands
Models, Molecular
Molecular Sequence Data
Nerve Tissue Proteins
Peptides
Phosphatidylinositol 4,5-Diphosphate
Proline
Protein Structure, Tertiary
Rats
Wiskott-Aldrich Syndrome
Wiskott-Aldrich Syndrome Protein, Neuronal
