6uzt
From Proteopedia
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(New page: '''Unreleased structure''' The entry 6uzt is ON HOLD Authors: Description: Category: Unreleased Structures) |
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- | '''Unreleased structure''' | ||
- | + | ==Crystal Structure of RPTP alpha== | |
+ | <StructureSection load='6uzt' size='340' side='right'caption='[[6uzt]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
+ | == Structural highlights == | ||
+ | <table><tr><td colspan='2'>[[6uzt]] is a 2 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=6UZT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6UZT 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]] 1.8Å</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=6uzt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6uzt OCA], [https://pdbe.org/6uzt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6uzt RCSB], [https://www.ebi.ac.uk/pdbsum/6uzt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6uzt ProSAT]</span></td></tr> | ||
+ | </table> | ||
+ | == Function == | ||
+ | [https://www.uniprot.org/uniprot/PTPRA_HUMAN PTPRA_HUMAN] Tyrosine protein phosphatase which is involved in integrin-mediated focal adhesion formation (By similarity). Following integrin engagement, specifically recruits BCAR3, BCAR1 and CRK to focal adhesions thereby promoting SRC-mediated phosphorylation of BRAC1 and the subsequent activation of PAK and small GTPase RAC1 and CDC42 (By similarity).[UniProtKB:P18052] | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | Receptor-type protein tyrosine phosphatase alpha (RPTPalpha) is an important positive regulator of SRC kinase activation and a known promoter of cancer growth, fibrosis, and arthritis. The domain structure of RPTPs comprises an extracellular region, a transmembrane helix, and two tandem intracellular catalytic domains referred as D1 and D2. The D2 domain of RPTPs is believed to mostly play a regulatory function; however, no regulatory model has been established for RPTPalpha-D2 or other RPTP-D2 domains. Here, we solved the 1.8 A resolution crystal structure of the cytoplasmic region of RPTPalpha, encompassing D1 and D2, trapped in a conformation that revealed a possible mechanism through which D2 can allosterically inhibit D1 activity. Using a D2-truncation RPTPalpha variant and mutational analysis of the D1/D2 interfaces, we show that D2 inhibits RPTPalpha phosphatase activity and identified a P405FTP408 motif in D1 that mediates the inhibitory effect of D2. Expression of the gain-of-function F406A/T407A RPTPalpha variant in HEK293T cells enhanced SRC activation, supporting the relevance of our proposed D2-mediated regulation mechanism in cell signaling. There is emerging interest in the development of allosteric inhibitors of RPTPs, but a scarcity of validated allosteric sites for RPTPs. The results of our study not only shed light on the regulatory role of RPTP-D2 domains, but also provide a potentially useful tool for the discovery of chemical probes targeting RPTPalpha and other RPTPs. | ||
- | + | RPTPalpha phosphatase activity is allosterically regulated by the membrane-distal catalytic domain.,Wen Y, Yang S, Wakabayashi K, Svensson MND, Stanford SM, Santelli E, Bottini N J Biol Chem. 2020 Mar 5. pii: RA119.011808. doi: 10.1074/jbc.RA119.011808. PMID:32139509<ref>PMID:32139509</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | [[Category: | + | </div> |
+ | <div class="pdbe-citations 6uzt" style="background-color:#fffaf0;"></div> | ||
+ | |||
+ | ==See Also== | ||
+ | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] | ||
+ | == References == | ||
+ | <references/> | ||
+ | __TOC__ | ||
+ | </StructureSection> | ||
+ | [[Category: Homo sapiens]] | ||
+ | [[Category: Large Structures]] | ||
+ | [[Category: Bottini N]] | ||
+ | [[Category: Santelli E]] | ||
+ | [[Category: Stanford SM]] | ||
+ | [[Category: Svensson MND]] | ||
+ | [[Category: Wen Y]] | ||
+ | [[Category: Yang S]] |
Current revision
Crystal Structure of RPTP alpha
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Categories: Homo sapiens | Large Structures | Bottini N | Santelli E | Stanford SM | Svensson MND | Wen Y | Yang S