|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Insights into structural integration of the PLCgamma regulatory region and mechanism of autoinhibition and activation based on key roles of SH2 domains== | | ==Insights into structural integration of the PLCgamma regulatory region and mechanism of autoinhibition and activation based on key roles of SH2 domains== |
| - | <StructureSection load='4fbn' size='340' side='right' caption='[[4fbn]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='4fbn' size='340' side='right'caption='[[4fbn]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4fbn]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FBN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FBN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4fbn]] is a 1 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=4FBN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FBN FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ey0|4ey0]]</td></tr> | + | </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=4fbn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fbn OCA], [https://pdbe.org/4fbn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fbn RCSB], [https://www.ebi.ac.uk/pdbsum/4fbn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fbn ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PLC1, PLCG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoinositide_phospholipase_C Phosphoinositide phospholipase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.11 3.1.4.11] </span></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=4fbn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fbn OCA], [http://pdbe.org/4fbn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4fbn RCSB], [http://www.ebi.ac.uk/pdbsum/4fbn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4fbn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PLCG1_HUMAN PLCG1_HUMAN]] Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration.<ref>PMID:17229814</ref> | + | [https://www.uniprot.org/uniprot/PLCG1_HUMAN PLCG1_HUMAN] Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration.<ref>PMID:17229814</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 27: |
Line 24: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Phosphoinositide phospholipase C]] | + | [[Category: Large Structures]] |
| - | [[Category: Bunney, T D]] | + | [[Category: Bunney TD]] |
| - | [[Category: Cole, A R]] | + | [[Category: Cole AR]] |
| - | [[Category: Katan, M]] | + | [[Category: Katan M]] |
| - | [[Category: Mas-Droux, C P]] | + | [[Category: Mas-Droux CP]] |
| - | [[Category: Fibroblast growth factor receptor 1]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Interaction domain]]
| + | |
| - | [[Category: Plcgamma specific array]]
| + | |
| - | [[Category: Sh2 domain]]
| + | |
| Structural highlights
Function
PLCG1_HUMAN Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration.[1]
Publication Abstract from PubMed
Multidomain proteins incorporating interaction domains are central to regulation of cellular processes. The elucidation of structural organization and mechanistic insights into many of these proteins, however, remain challenging due to their inherent flexibility. Here, we describe the organization and function of four interaction domains in PLCgamma1 using a combination of structural biology and biochemical approaches. Intramolecular interactions within the regulatory region center on the cSH2 domain, the only domain that also interacts with the PLC-core. In the context of fibroblast growth-factor receptor signaling, the coordinated involvement of nSH2 and cSH2 domains mediates efficient phosphorylation of PLCgamma1 resulting in the interruption of an autoinhibitory interface by direct competition and, independently, dissociation of PLCgamma1 from the receptor. Further structural insights into the autoinhibitory surfaces provide a framework to interpret gain-of-function mutations in PLCgamma isoforms linked to immune disorders and illustrate a distinct mechanism for regulation of PLC activity by common interaction domains.
Structural and functional integration of the PLCgamma interaction domains critical for regulatory mechanisms and signaling deregulation.,Bunney TD, Esposito D, Mas-Droux C, Lamber E, Baxendale RW, Martins M, Cole A, Svergun D, Driscoll PC, Katan M Structure. 2012 Dec 5;20(12):2062-75. doi: 10.1016/j.str.2012.09.005. Epub 2012, Oct 11. PMID:23063561[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Wang Y, Tomar A, George SP, Khurana S. Obligatory role for phospholipase C-gamma(1) in villin-induced epithelial cell migration. Am J Physiol Cell Physiol. 2007 May;292(5):C1775-86. Epub 2007 Jan 17. PMID:17229814 doi:10.1152/ajpcell.00420.2006
- ↑ Bunney TD, Esposito D, Mas-Droux C, Lamber E, Baxendale RW, Martins M, Cole A, Svergun D, Driscoll PC, Katan M. Structural and functional integration of the PLCgamma interaction domains critical for regulatory mechanisms and signaling deregulation. Structure. 2012 Dec 5;20(12):2062-75. doi: 10.1016/j.str.2012.09.005. Epub 2012, Oct 11. PMID:23063561 doi:10.1016/j.str.2012.09.005
|
