2ksp

<StructureSection load='2ksp' size='340' side='right'caption='[[2ksp]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>

<table><tr><td colspan='2'>[[2ksp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KSP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KSP FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">EHD1, PAST, PAST1, CDABP0131 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ksp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ksp OCA], [http://pdbe.org/2ksp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ksp RCSB], [http://www.ebi.ac.uk/pdbsum/2ksp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ksp ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/EHD1_HUMAN EHD1_HUMAN]] Acts in early endocytic membrane fusion and membrane trafficking of recycling endosomes.<ref>PMID:15020713</ref> <ref>PMID:17233914</ref> [[http://www.uniprot.org/uniprot/MILK1_HUMAN MILK1_HUMAN]] Probable lipid-binding protein with higher affinity for phosphatidic acid, a lipid enriched in recycling endosome membranes. On endosome membranes, may act as a downstream effector of Rab proteins recruiting cytosolic proteins to regulate membrane tubulation. May be involved in a late step of receptor-mediated endocytosis regulating for instance endocytosed-EGF receptor trafficking. Alternatively, may regulate slow endocytic recycling of endocytosed proteins back to the plasma membrane. May indirectly play a role in neurite outgrowth.<ref>PMID:21795389</ref> <ref>PMID:19864458</ref> <ref>PMID:20801876</ref> <ref>PMID:23596323</ref>

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== Publication Abstract from PubMed ==

Epidermal growth factor receptor tyrosine kinase substrate 15 (Eps15) homology (EH)-domain proteins can be divided into two classes: those with an N-terminal EH-domain(s), and the C-terminal Eps15 homology domain-containing proteins (EHDs). Whereas many N-terminal EH-domain proteins regulate internalization events, the best characterized C-terminal EHD, EHD1, regulates endocytic recycling. Because EH-domains interact with the tripeptide Asn-Pro-Phe (NPF), it is of critical importance to elucidate the molecular mechanisms that allow EHD1 and its paralogs to interact selectively with a subset of the hundreds of NPF-containing proteins expressed in mammalian cells. Here, we capitalize on our findings that C-terminal EH-domains possess highly positively charged interaction surfaces and that many NPF-containing proteins that interact with C-terminal (but not N-terminal) EH-domains are followed by acidic residues. Using the recently identified EHD1 interaction partner molecule interacting with CasL (MICAL)-Like 1 (MICAL-L1) as a model, we have demonstrated that only the first of its two NPF motifs is required for EHD1 binding. Because only this first NPF is followed by acidic residues, we have utilized glutathione S-transferase pulldowns, two-hybrid analysis, and NMR to demonstrate that the flanking acidic residues "fine tune" the binding affinity to EHD1. Indeed, our NMR solution structure of the EHD1 EH-domain in complex with the MICAL-L1 NPFEEEEED peptide indicates that the first two flanking Glu residues lie in a position favorable to form salt bridges with Lys residues within the EH-domain. Our data provide a novel explanation for the selective interaction of C-terminal EH-domains with specific NPF-containing proteins and allow for the prediction of new interaction partners with C-terminal EHDs.

Mechanism for the selective interaction of C-terminal Eps15 homology domain proteins with specific Asn-Pro-Phe-containing partners.,Kieken F, Sharma M, Jovic M, Giridharan SS, Naslavsky N, Caplan S, Sorgen PL J Biol Chem. 2010 Mar 19;285(12):8687-94. Epub 2010 Jan 27. PMID:20106972<ref>PMID:20106972</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 2ksp" style="background-color:#fffaf0;"></div>

[[Category: Human]]

[[Category: Caplan, S]]

[[Category: Giridharan, S S]]

[[Category: Jovic, M]]

[[Category: Kieken, F]]

[[Category: Naslavsky, N]]

[[Category: Sharma, M]]

[[Category: Sorgen, P L]]

[[Category: Protein-protein interaction]]