|
|
| (2 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Phosphotyrosine binding domain== | | ==Phosphotyrosine binding domain== |
| - | <StructureSection load='2mq1' size='340' side='right'caption='[[2mq1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mq1' size='340' side='right'caption='[[2mq1]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mq1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MQ1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MQ1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mq1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MQ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MQ1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cbll1, Hakai ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2mq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mq1 OCA], [http://pdbe.org/2mq1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mq1 RCSB], [http://www.ebi.ac.uk/pdbsum/2mq1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mq1 ProSAT]</span></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=2mq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mq1 OCA], [https://pdbe.org/2mq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mq1 RCSB], [https://www.ebi.ac.uk/pdbsum/2mq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mq1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HAKAI_MOUSE HAKAI_MOUSE]] Promotes ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1. Targets CDH1 for endocytosis and degradation.<ref>PMID:11836526</ref> <ref>PMID:22252131</ref> | + | [https://www.uniprot.org/uniprot/HAKAI_MOUSE HAKAI_MOUSE] Promotes ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1. Targets CDH1 for endocytosis and degradation.<ref>PMID:11836526</ref> <ref>PMID:22252131</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 21: |
Line 21: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin protein ligase|Ubiquitin protein ligase]] | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 27: |
Line 27: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Jing-Song, F]] | + | [[Category: Jing-Song F]] |
| - | [[Category: Mukherjee, M]] | + | [[Category: Mukherjee M]] |
| - | [[Category: Sivaraman, J]] | + | [[Category: Sivaraman J]] |
| - | [[Category: Ligase]]
| + | |
| - | [[Category: Phosphotyrosine binding]]
| + | |
| Structural highlights
Function
HAKAI_MOUSE Promotes ubiquitination of several tyrosine-phosphorylated Src substrates, including CDH1, CTTN and DOK1. Targets CDH1 for endocytosis and degradation.[1] [2]
Publication Abstract from PubMed
Hakai, an E3 ubiquitin ligase, disrupts cell-cell contacts in epithelial cells and is up-regulated in human colon and gastric adenocarcinomas. Hakai acts through its phosphotyrosine-binding (HYB) domain, which bears a dimeric fold that recognizes the phosphotyrosine motifs of E-cadherin, cortactin, DOK1, and other Src substrates. Unlike the monomeric nature of the SH2 and phosphotyrosine-binding domains, the architecture of the HYB domain consists of an atypical, zinc-coordinated tight homodimer. Here, we report a C-terminal truncation mutant of the HYB domain (HYB(DeltaC)), comprising amino acids 106-194, which exists as a monomer in solution. The NMR structure revealed that this deletion mutant undergoes a dramatic structural change caused by a rearrangement of the atypical zinc-coordinated unit in the C terminus of the HYB domain to a C2H2-like zinc finger in HYB(DeltaC). Moreover, using isothermal titration calorimetry, we show that dimerization of HYB(DeltaC) can be induced using a phosphotyrosine substrate peptide. This ligand-induced dimerization of HYB(DeltaC) is further validated using analytical ultracentrifugation, size-exclusion chromatography, NMR relaxation studies, dynamic light scattering, and circular dichroism experiments. Overall, these observations suggest that the dimeric architecture of the HYB domain is essential for the phosphotyrosine-binding property of Hakai.
Dimeric switch of Hakai-truncated monomers during substrate recognition: insights from solution studies and NMR structure.,Mukherjee M, Jing-Song F, Ramachandran S, Guy GR, Sivaraman J J Biol Chem. 2014 Sep 12;289(37):25611-23. doi: 10.1074/jbc.M114.592840. Epub, 2014 Jul 29. PMID:25074933[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fujita Y, Krause G, Scheffner M, Zechner D, Leddy HE, Behrens J, Sommer T, Birchmeier W. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. Nat Cell Biol. 2002 Mar;4(3):222-31. PMID:11836526 doi:10.1038/ncb758
- ↑ Mukherjee M, Chow SY, Yusoff P, Seetharaman J, Ng C, Sinniah S, Koh XW, Asgar NF, Li D, Yim D, Jackson RA, Yew J, Qian J, Iyu A, Lim YP, Zhou X, Sze SK, Guy GR, Sivaraman J. Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin. EMBO J. 2012 Jan 17;31(5):1308-19. doi: 10.1038/emboj.2011.496. PMID:22252131 doi:10.1038/emboj.2011.496
- ↑ Mukherjee M, Jing-Song F, Ramachandran S, Guy GR, Sivaraman J. Dimeric switch of Hakai-truncated monomers during substrate recognition: insights from solution studies and NMR structure. J Biol Chem. 2014 Sep 12;289(37):25611-23. doi: 10.1074/jbc.M114.592840. Epub, 2014 Jul 29. PMID:25074933 doi:http://dx.doi.org/10.1074/jbc.M114.592840
|
