 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
| Callebaut I | | An EVH1/WH1 domain as a key actor in TGFbeta signalling. | | FEBS Lett 2002 May 22;519(1) : 178-80. | | PMID: 12023040 |
| 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 |
| Tu JC, Xiao B, Naisbitt S, Yuan JP, Petralia RS, Brakeman P, Doan A, Aakalu VK, Lanahan AA, Sheng M, Worley PF | | Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of
postsynaptic density proteins. | | Neuron 1999 Jul;23(3) : 583-92. | | PMID: 10433269 |
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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signal transduction
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metabotropic glutamate receptor signaling pathway
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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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signal transducer |
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glutamate receptor |
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receptor signaling protein |
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