Aromatic and basic residues within the EVH1 domain of VASP specify its interaction with proline-rich ligands
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 dist...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2014
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| Online Access: | http://hdl.handle.net/1721.1/83930 https://orcid.org/0000-0003-3214-4554 |
| _version_ | 1826191287763599360 |
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| author | Carl, Uwe D. Pollmann, Marc Orr, Elisha Chakraborty, Trinad Wehland, Juergen Gertler, Frank |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Carl, Uwe D. Pollmann, Marc Orr, Elisha Chakraborty, Trinad Wehland, Juergen Gertler, Frank |
| author_sort | Carl, Uwe D. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:53:31Z |
| format | Article |
| id | mit-1721.1/83930 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:53:31Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/839302022-09-26T08:58:13Z Aromatic and basic residues within the EVH1 domain of VASP specify its interaction with proline-rich ligands Carl, Uwe D. Pollmann, Marc Orr, Elisha Chakraborty, Trinad Wehland, Juergen Gertler, Frank Massachusetts Institute of Technology. Department of Biology Gertler, Frank 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. Merck & Co., Inc. 2014-01-13T20:30:22Z 2014-01-13T20:30:22Z 1999-07 1999-05 Article http://purl.org/eprint/type/JournalArticle 09609822 1879-0445 http://hdl.handle.net/1721.1/83930 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. https://orcid.org/0000-0003-3214-4554 en_US http://dx.doi.org/10.1016/S0960-9822(99)80315-7 Current Biology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | Carl, Uwe D. Pollmann, Marc Orr, Elisha Chakraborty, Trinad Wehland, Juergen Gertler, Frank Aromatic and basic residues within the EVH1 domain of VASP specify its interaction with proline-rich ligands |
| title | Aromatic and basic residues within the EVH1 domain of VASP specify its interaction with proline-rich ligands |
| title_full | Aromatic and basic residues within the EVH1 domain of VASP specify its interaction with proline-rich ligands |
| title_fullStr | Aromatic and basic residues within the EVH1 domain of VASP specify its interaction with proline-rich ligands |
| title_full_unstemmed | Aromatic and basic residues within the EVH1 domain of VASP specify its interaction with proline-rich ligands |
| title_short | Aromatic and basic residues within the EVH1 domain of VASP specify its interaction with proline-rich ligands |
| title_sort | aromatic and basic residues within the evh1 domain of vasp specify its interaction with proline rich ligands |
| url | http://hdl.handle.net/1721.1/83930 https://orcid.org/0000-0003-3214-4554 |
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