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Published on: May 5, 2020
Multiple WASP-interacting protein recognition motifs are required for a functional interaction with N-WASP
Francis C Peterson1, Qing Deng, Markus Zettl
1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
The Journal of Biological Chemistry
|January 19, 2007
Summary
The WASP-interacting protein (WIP) binds to the N-WASP EVH1 domain via an extended interface. This interaction involves a reversed polyproline motif and additional hydrophobic contacts, crucial for cellular binding.
Area of Science:
- Molecular Biology
- Protein-Protein Interactions
- Structural Biology
Background:
- WASP-interacting protein (WIP) interacts with WASP/WAVE proteins via the enabled/VASP homology (EVH1) domain.
- Previous studies identified two N-WASP binding motifs within WIP residues 451-485 and determined the structure of a WIP-(461-485)/N-WASP EVH1 complex.
Purpose of the Study:
- To elucidate the structural basis of the extended WIP-N-WASP interaction.
- To characterize the functional significance of the entire WIP binding domain.
Main Methods:
- X-ray crystallography to determine the structure of the WIP-(461-485)/N-WASP EVH1 complex.
- Analysis of sequence conservation in verprolin family proteins.
- Cellular assays to assess the impact of epitope disruption on N-WASP binding.
Main Results:
- The combined WIP-(451-485) sequence extends the previously observed interface with the N-WASP EVH1 domain.
- A central polyproline motif binds in a reversed orientation within the canonical EVH1 site.
- Additional hydrophobic contacts and three distinct WIP epitopes contribute to the interaction, forming a significantly longer binding domain than typical polyproline motifs.
Conclusions:
- The WIP-N-WASP interaction involves an extended binding interface beyond the canonical polyproline motif.
- Multiple specific contacts and a reversed polyproline orientation characterize this interaction.
- The entire WIP binding domain is functionally important for N-WASP binding in cells.
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