 Abstract
Enabled/vasodilator-stimulated phosphoprotein homology 1 (EVH1) domains are 115 residue protein-protein interaction modules which provide essential links for their host proteins to various signal transduction pathways. Many EVH1-containing proteins are associated closely with actin-based structures and are involved in re-organization of the actin cytoskeleton. EVH1 domains are also present in proteins enriched in neuronal tissue, thus implicating them as potential mediators of synaptic plasticity, linking them to memory formation and learning. EVH1 domains recognize and bind specific prolin-rich sequences (PRSs). In general, a small (3-6 residue) core PRS in the target protein binds a 'recognition pocket' on the domain surface. Further affinity - and specificity -increasing interactions are then formed between additional domain epitopes and peptide 'core-flanking' residues.
The protein-protein interactions mediated by EVH1 domains are clearly higly important for the regulation of signal transduction events, re-organization of the actin cytoskeleton, and modulation of actin dynamics and actin-based motility.
EVH1 domains can be divided into two classes based on the consesus sequences of their target PRS ligands. Single residue peptide substitution experiments have shown the consensus binding motif for class I EVH1 domains to be F-P-X-(hydrofphobic)-P. Such sequences are found in a number of mammalian proteins, including the focal adhesion proteins zyxin and viniculin, as well as in the ActA protein of the intracellular pathogen Listeria monocytogenes.
Class II EVH1 domains are found in the Homer-Vesl protein family of postsynaptic receptor associated proteins. These recognize a consensus PRS, with a core motif comprising PPxxF, found in the group I mGluRs, IP3Rs, RyRs and the Shank family proteins.
Selected references
| Ball LJ, Kuhne R, Hoffmann B, Hafner A, Schmieder P, Volkmer-Engert R, Hof M, Wahl M, Schneider-Mergener J, Walter U, Oschkinat H, Jarchau T | | Dual epitope recognition by the VASP EVH1 domain modulates polyproline
ligand specificity and binding affinity. | | EMBO J 2000 Sep 15;19(18) : 4903-14. | | PMID: 10990454 |
| Callebaut I | | An EVH1/WH1 domain as a key actor in TGFbeta signalling. | | FEBS Lett 2002 May 22;519(1) : 178-80. | | PMID: 12023040 |
| Fedorov AA, Fedorov E, Gertler F, Almo SC | | Structure of EVH1, a novel proline-rich ligand-binding module involved in
cytoskeletal dynamics and neural function. | | Nat Struct Biol 1999 Jul;6(7) : 661-5. | | PMID: 10404224 |
| Prehoda KE, Lee DJ, Lim WA | | Structure of the enabled/VASP homology 1 domain-peptide complex: a key
component in the spatial control of actin assembly. | | Cell 1999 May 14;97(4) : 471-80. | | PMID: 10338211 |
| Renfranz PJ, Beckerle MC | | Doing (F/L)PPPPs: EVH1 domains and their proline-rich partners in cell
polarity and migration. | | Curr Opin Cell Biol 2002 Feb;14(1) : 88-103. | | PMID: 11792550 |
This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.
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Biological Process |
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cell growth and/or maintenance
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signal transduction
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cytoskeletal regulator
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actin filament polymerization
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positive regulation of actin polymerization and/or depolymerization
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Cellular Component |
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plasma membrane |
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cytosol |
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Molecular Function |
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Binding |
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protein binding |
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protein domain specific binding |
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