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Multiple WASP-interacting protein recognition motifs are required for a functional interaction with N-WASP. J Biol Chem 2007 Mar 16;282(11):8446-53 PMID: 17229736

Abstract

The WASP-interacting protein (WIP) targets WASP/WAVE proteins through a constitutive interaction with an amino-terminal enabled/VASP homology (EVH1) domain. Parallel investigations had previously identified two distinct N-WASP binding motifs corresponding to WIP residues 451-461 and 461-485, and we determined the structure of a complex between WIP-(461-485) and the N-WASP EVH1 domain (Volkman, B. F., Prehoda, K. E., Scott, J. A., Peterson, F. C., and Lim, W. A. (2002) Cell 111, 565-576). The present results show that, when combined, the WIP-(451-485) sequence wraps further around the EVH1 domain, extending the interface observed previously. Specific contacts with three WIP epitopes corresponded to regions of high sequence conservation in the verprolin family. A central polyproline motif occupied the canonical binding site but in a reversed orientation relative to other EVH1 complexes. This interaction was augmented in the amino- and carboxyl-terminal directions by additional hydrophobic contacts involving WIP residues 454-459 and 475-478, respectively. Disruption of any of the three WIP epitopes reduced N-WASP binding in cells, demonstrating a functional requirement for the entire binding domain, which is significantly longer than the polyproline motifs recognized by other EVH1 domains.

Author List

Peterson FC, Deng Q, Zettl M, Prehoda KE, Lim WA, Way M, Volkman BF

Authors

Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of Wisconsin
Brian 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 Motifs
Amino Acid Sequence
Animals
Carrier Proteins
Cytoskeletal Proteins
Epitopes
Intracellular Signaling Peptides and Proteins
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Sequence Data
Peptides
Protein Binding
Protein Conformation
Protein Structure, Tertiary
Rats
Sequence Homology, Amino Acid
Wiskott-Aldrich Syndrome Protein, Neuronal

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View this publication's entry at the Pubmed website PMID: 17229736