1c07
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Categories: Homo sapiens | Single protein | Beer, T.De. | Enmon, J.L. | Overduin, M. | CA | Calcium binding | Ef-hand | Eh domain | Fw binding | Npf binding | Signaling domain | Signaling protein
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(New page: 200px<br /> <applet load="1c07" size="450" color="white" frame="true" align="right" spinBox="true" caption="1c07" /> '''STRUCTURE OF THE THIRD EPS15 HOMOLOGY DOMAI...)
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Revision as of 14:09, 12 November 2007
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STRUCTURE OF THE THIRD EPS15 HOMOLOGY DOMAIN OF HUMAN EPS15
Overview
Eps15 homology (EH) domains interact with proteins involved in endocytosis, and signal transduction. EH domains bind to Asn-Pro-Phe (NPF) consensus, motifs of target proteins. A few EH domains, such as the third EH domain, (EH(3)) of human Eps15, prefer to bind Phe-Trp (FW) sequences. The, structure of EH(3) has been solved by nuclear magnetic resonance (NMR), spectroscopy and is the first of an FW- and NPF-binding EH domain. Both FW, and NPF sequences bind in the same hydrophobic pocket as shown by, heteronuclear chemical shift mapping. EH(3) contains the dual EF-hand fold, characteristic of the EH domain family, but it binds calcium with high, affinity in the first EF-hand rather than the usual coordination in the, second EF-hand. Point mutations were designed based on differences in the, EH(3) and the second EH domain (EH(2)) of human Eps15 that alter the, affinity of the domains for FW or NPF motif peptides. Peptides that mimic, binding sites in the potential EH(3) targets Rab, synaptojanin, and the, cation-dependent mannose 6-phosphate receptor were used to explore, wild-type and mutant affinities. Characterization of the structure and, binding properties of an FW- and NPF-binding EH domain and comparison to, an NPF-specific EH domain provide important insights into the mechanisms, of EH domain ligand recognition.
About this Structure
1C07 is a Single protein structure of sequence from Homo sapiens with CA as ligand. Full crystallographic information is available from OCA.
Reference
Solution structure of Eps15's third EH domain reveals coincident Phe-Trp and Asn-Pro-Phe binding sites., Enmon JL, de Beer T, Overduin M, Biochemistry. 2000 Apr 18;39(15):4309-19. PMID:10757979
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