4tkn
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4tkn is ON HOLD Authors: Stiegler, A.L., Zhang, R., Liu, W., Boggon, T.J. Description:) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Structure of the SNX17 FERM domain bound to the second NPxF motif of KRIT1== | |
| + | <StructureSection load='4tkn' size='340' side='right'caption='[[4tkn]], [[Resolution|resolution]] 3.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4tkn]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TKN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TKN FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4tkn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tkn OCA], [https://pdbe.org/4tkn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tkn RCSB], [https://www.ebi.ac.uk/pdbsum/4tkn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tkn ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SNX17_HUMAN SNX17_HUMAN] Critical regulator of endosomal recycling of numerous receptors, channels, and other transmembrane proteins. Binds to NPxY sequences in the cytoplasmic tails of target cargos. Plays a role in the sorting of endocytosed LRP1 and APP, and prevents their degradation. Required for maintenance of normal cell surface levels of APP and LRP1. Recycles internalized integrins ITGB1, ITGB5 and their associated alpha subunits, preventing them from lysosomal degradation. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)).<ref>PMID:15121882</ref> <ref>PMID:15769472</ref> <ref>PMID:16712798</ref> <ref>PMID:19005208</ref> <ref>PMID:22492727</ref> <ref>PMID:21512128</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Sorting nexin 17 (SNX17) is a member of the family of cytoplasmic sorting nexin adaptor proteins that regulate endosomal trafficking of cell surface proteins. SNX17 localizes to early endosomes where it directly binds NPxY/F motifs in the cytoplasmic tails of its target receptors to mediate their rates of endocytic internalization, recycling, and/or degradation. SNX17 has also been implicated in mediating cell signaling and can interact with cytoplasmic proteins. Krev interaction trapped 1 (KRIT1), a cytoplasmic adaptor protein associated with cerebral cavernous malformations (CCM), has previously been shown to interact with SNX17. Here, we demonstrate that SNX17 indeed binds directly to KRIT1 and map the binding to the second Asn-Pro-x-Tyr/Phe (NPxY/F) motif in KRIT1. We further characterize the interaction as being mediated by the FERM domain of SNX17. We present the co-crystal structure of SNX17-FERM with the KRIT1-NPxF2 peptide to 3.0 A resolution, and demonstrate that the interaction is highly similar in structure and binding affinity to that between SNX17 and p-selectin. We verify the molecular details of the interaction by site directed mutagenesis and pull down assay, and thereby confirm that the major binding site for SNX17 is confined to the NPxF2 motif in KRIT1. Taken together, our results verify a direct interaction between SNX17 and KRIT1 and classify KRIT1 as a SNX17 binding partner. | ||
| - | + | Structural determinants for binding of Sorting Nexin 17 (SNX17) to the cytoplasmic adaptor protein Krev Interaction Trapped 1 (KRIT1)*,Stiegler AL, Zhang R, Liu W, Boggon TJ J Biol Chem. 2014 Jul 24. pii: jbc.M114.584011. PMID:25059659<ref>PMID:25059659</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4tkn" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Sorting nexin 3D structures|Sorting nexin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Boggon TJ]] | ||
| + | [[Category: Liu W]] | ||
| + | [[Category: Stiegler AL]] | ||
| + | [[Category: Zhang R]] | ||
Current revision
Structure of the SNX17 FERM domain bound to the second NPxF motif of KRIT1
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