Aromatic and basic residues within the EVH1 domain of VASP specify its interaction with proline-rich ligands
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Author(s)
Carl, Uwe D.
Pollmann, Marc
Orr, Elisha
Chakraborty, Trinad
Wehland, Juergen
Gertler, Frank
Date Issued
July 1999
Journal
Current Biology
Publisher
Elsevier
Citation
Carl, Uwe D., Marc Pollmann, Elisha Orr, Frank B. Gertler, Trinad Chakraborty, and Juergen Wehland. “Aromatic and basic residues within the EVH1 domain of VASP specify its interaction with proline-rich ligands.” Current Biology 9, no. 13 (July 1999): 715-S4. Copyright © 1999 Elsevier Science Ltd.
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Final published version
Abstract
Short contiguous peptides harboring proline-rich motifs are frequently involved in protein–protein interactions, such as associations with Src homology 3 (SH3) and WW domains. Although patches of aromatic residues present in either domain interact with polyprolines, their overall structures are distinct, suggesting that additional protein families exist that use stacked aromatic amino acids (AA domains) to bind polyproline motifs [1], [2] and [3]. A polyproline motif (E/DFPPPPTD/E in the single-letter amino-acid code), present in the ActA protein of the intracellular bacterial pathogen Listeria monocytogenes, serves as a ligand for the Ena/VASP protein family – the vasodilator-stimulated phosphoprotein (VASP), the murine protein Mena, Drosophila Enabled (Ena) and the Ena/VASP-like protein Evl [4], [5], [6] and [7]. These share a similar overall structure characterized by the two highly conserved Ena/VASP homology domains (EVH1 and EVH2) [5]. Here, using three independent assays, we have delineated the minimal EVH1 domain. Mutations of aromatic and basic residues within two conserved hydrophilic regions of the EVH1 domain abolished binding to ActA. Binding of an EVH1 mutant with reversed charges could partially be rescued by introducing complementary mutations within the ligand. Like SH3 domains, aromatic residues within the EVH1 domain interacted with polyprolines, whereas the ligand specificity of either domain was determined by reciprocally charged residues. The EVH1 domain is therefore a new addition to the AA domain superfamily, which includes SH3 and WW domains.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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DOI of Published Version
https://doi.org/10.1016/S0960-9822(99)80315-7
