EVH1 domains: structure, function and interactions.
Drosophila 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. Like Src homology 3, WW and GYF domains and profilin, EVH1 domains recognize and bind specific proline-rich sequences (PRSs). The binding is of low affinity, but tightly regulated by the high specificity encoded into residues in the protein:peptide interface. 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 three-dimensional structures of EVH1:peptide complexes now reveal, in great detail, some of the most important features of these interactions and allow us to better understand the origins of specificity, ligand orientation and sequence degeneracy of target peptides, in low affinity signalling complexes.
Ball
Linda J
LJ
Forschunginstitut für Molekulare Pharmacologie, Campus Berlin-Buch, Berlin, Germany. linda@fmp-berlin.de
Jarchau
Thomas
T
Oschkinat
Hartmut
H
Walter
Ulrich
U
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016384:Consensus Sequence; D004330:Drosophila; D019476:Insect Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D011392:Proline / Q000378:metabolism; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D019476:Insect Proteins; D009419:Nerve Tissue Proteins; D011392:Proline