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| | ==Crystal structure of a phosphotyrosine binding domain== | | ==Crystal structure of a phosphotyrosine binding domain== |
| - | <StructureSection load='3vk6' size='340' side='right' caption='[[3vk6]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='3vk6' size='340' side='right'caption='[[3vk6]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3vk6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VK6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VK6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3vk6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VK6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VK6 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">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</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 Mus musculus])</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=3vk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vk6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vk6 RCSB], [http://www.ebi.ac.uk/pdbsum/3vk6 PDBsum]</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=3vk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vk6 OCA], [https://pdbe.org/3vk6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vk6 RCSB], [https://www.ebi.ac.uk/pdbsum/3vk6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vk6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [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> |
| - | Phosphotyrosine-binding domains, typified by the SH2 (Src homology 2) and PTB domains, are critical upstream components of signal transduction pathways. The E3 ubiquitin ligase Hakai targets tyrosine-phosphorylated E-cadherin via an uncharacterized domain. In this study, the crystal structure of Hakai (amino acids 106-206) revealed that it forms an atypical, zinc-coordinated homodimer by utilizing residues from the phosphotyrosine-binding domain of two Hakai monomers. Hakai dimerization allows the formation of a phosphotyrosine-binding pocket that recognizes specific phosphorylated tyrosines and flanking acidic amino acids of Src substrates, such as E-cadherin, cortactin and DOK1. NMR and mutational analysis identified the Hakai residues required for target binding within the binding pocket, now named the HYB domain. ZNF645 also possesses a HYB domain but demonstrates different target specificities. The HYB domain is structurally different from other phosphotyrosine-binding domains and is a potential drug target due to its novel structural features.
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| - | Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin.,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 EMBO J. 2012 Jan 17;31(5):1308-19. doi: 10.1038/emboj.2011.496. PMID:22252131<ref>PMID:22252131</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div> | + | |
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| | ==See Also== | | ==See Also== |
| - | *[[Ubiquitin protein ligase|Ubiquitin protein ligase]] | + | *[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Mukherjee, M]] | + | [[Category: Mukherjee M]] |
| - | [[Category: Sivaraman, J]] | + | [[Category: Sivaraman J]] |
| - | [[Category: Hyb]]
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| - | [[Category: Ligase]]
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| - | [[Category: Phosphotyrosine binding domain]]
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| 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]
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
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