6y23
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==DDR1 kinase autoinhibited by its juxtamembrane region== | |
| + | <StructureSection load='6y23' size='340' side='right'caption='[[6y23]], [[Resolution|resolution]] 2.58Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6y23]] is a 3 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=6Y23 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y23 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]] 2.58Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6y23 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y23 OCA], [https://pdbe.org/6y23 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y23 RCSB], [https://www.ebi.ac.uk/pdbsum/6y23 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y23 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/DDR1_HUMAN DDR1_HUMAN] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Discoidin domain receptor 1 (DDR1) is a collagen-activated receptor tyrosine kinase with important functions in organogenesis and tissue homeostasis. Aberrant DDR1 activity contributes to the progression of human diseases, including fibrosis and cancer. How DDR1 activity is regulated is poorly understood. We investigated the function of the long intracellular juxtamembrane (JM) region of human DDR1 and found that the kinase-proximal segment, JM4, is an important regulator of kinase activity. Crystal structure analysis revealed that JM4 forms a hairpin that penetrates the kinase active site, reinforcing autoinhibition by the activation loop. Using in vitro enzymology with soluble kinase constructs, we established that release from autoinhibition occurs in two distinct steps: rapid autophosphorylation of the JM4 tyrosines, Tyr569 and Tyr586, followed by slower autophosphorylation of activation loop tyrosines. Mutation of JM4 tyrosines abolished collagen-induced DDR1 activation in cells. The insights may be used to develop allosteric, DDR1-specific, kinase inhibitors. | ||
| - | + | Two-step release of kinase autoinhibition in discoidin domain receptor 1.,Sammon D, Hohenester E, Leitinger B Proc Natl Acad Sci U S A. 2020 Sep 8;117(36):22051-22060. doi:, 10.1073/pnas.2007271117. Epub 2020 Aug 24. PMID:32839343<ref>PMID:32839343</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6y23" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Epithelial discoidin domain-containing receptor|Epithelial discoidin domain-containing receptor]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Hohenester E]] | ||
| + | [[Category: Leitinger B]] | ||
| + | [[Category: Sammon D]] | ||
Current revision
DDR1 kinase autoinhibited by its juxtamembrane region
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