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| | <StructureSection load='5gni' size='340' side='right'caption='[[5gni]], [[Resolution|resolution]] 3.01Å' scene=''> | | <StructureSection load='5gni' size='340' side='right'caption='[[5gni]], [[Resolution|resolution]] 3.01Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5gni]] is a 2 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=5GNI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5GNI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5gni]] 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=5GNI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GNI FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PECAM1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 3.008Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5gni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gni OCA], [http://pdbe.org/5gni PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5gni RCSB], [http://www.ebi.ac.uk/pdbsum/5gni PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5gni 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=5gni FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5gni OCA], [https://pdbe.org/5gni PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5gni RCSB], [https://www.ebi.ac.uk/pdbsum/5gni PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5gni ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PECA1_HUMAN PECA1_HUMAN]] Induces susceptibility to atherosclerosis (By similarity). Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions. Tyr-690 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes. Prevents phagocyte ingestion of closely apposed viable cells by transmitting 'detachment' signals, and changes function on apoptosis, promoting tethering of dying cells to phagocytes (the encounter of a viable cell with a phagocyte via the homophilic interaction of PECAM1 on both cell surfaces leads to the viable cell's active repulsion from the phagocyte. During apoptosis, the inside-out signaling of PECAM1 is somehow disabled so that the apoptotic cell does not actively reject the phagocyte anymore. The lack of this repulsion signal together with the interaction of the eat-me signals and their respective receptors causes the attachment of the apoptotic cell to the phagocyte, thus triggering the process of engulfment). Isoform Delta15 is unable to protect against apoptosis. Modulates BDKRB2 activation. Regulates bradykinin- and hyperosmotic shock-induced ERK1/2 activation in human umbilical cord vein cells (HUVEC).<ref>PMID:12110892</ref> <ref>PMID:18388311</ref> <ref>PMID:19342684</ref> | + | [https://www.uniprot.org/uniprot/PECA1_HUMAN PECA1_HUMAN] Induces susceptibility to atherosclerosis (By similarity). Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions. Tyr-690 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes. Prevents phagocyte ingestion of closely apposed viable cells by transmitting 'detachment' signals, and changes function on apoptosis, promoting tethering of dying cells to phagocytes (the encounter of a viable cell with a phagocyte via the homophilic interaction of PECAM1 on both cell surfaces leads to the viable cell's active repulsion from the phagocyte. During apoptosis, the inside-out signaling of PECAM1 is somehow disabled so that the apoptotic cell does not actively reject the phagocyte anymore. The lack of this repulsion signal together with the interaction of the eat-me signals and their respective receptors causes the attachment of the apoptotic cell to the phagocyte, thus triggering the process of engulfment). Isoform Delta15 is unable to protect against apoptosis. Modulates BDKRB2 activation. Regulates bradykinin- and hyperosmotic shock-induced ERK1/2 activation in human umbilical cord vein cells (HUVEC).<ref>PMID:12110892</ref> <ref>PMID:18388311</ref> <ref>PMID:19342684</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hao, Q]] | + | [[Category: Hao Q]] |
| - | [[Category: Hu, M]] | + | [[Category: Hu M]] |
| - | [[Category: Liu, Q]] | + | [[Category: Liu Q]] |
| - | [[Category: Zhang, H]] | + | [[Category: Zhang H]] |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Cell adhesion molecule]]
| + | |
| - | [[Category: Immunoglobulin-like domain]]
| + | |
| - | [[Category: Trans-homophilic dimer]]
| + | |
| Structural highlights
Function
PECA1_HUMAN Induces susceptibility to atherosclerosis (By similarity). Cell adhesion molecule which is required for leukocyte transendothelial migration (TEM) under most inflammatory conditions. Tyr-690 plays a critical role in TEM and is required for efficient trafficking of PECAM1 to and from the lateral border recycling compartment (LBRC) and is also essential for the LBRC membrane to be targeted around migrating leukocytes. Prevents phagocyte ingestion of closely apposed viable cells by transmitting 'detachment' signals, and changes function on apoptosis, promoting tethering of dying cells to phagocytes (the encounter of a viable cell with a phagocyte via the homophilic interaction of PECAM1 on both cell surfaces leads to the viable cell's active repulsion from the phagocyte. During apoptosis, the inside-out signaling of PECAM1 is somehow disabled so that the apoptotic cell does not actively reject the phagocyte anymore. The lack of this repulsion signal together with the interaction of the eat-me signals and their respective receptors causes the attachment of the apoptotic cell to the phagocyte, thus triggering the process of engulfment). Isoform Delta15 is unable to protect against apoptosis. Modulates BDKRB2 activation. Regulates bradykinin- and hyperosmotic shock-induced ERK1/2 activation in human umbilical cord vein cells (HUVEC).[1] [2] [3]
Publication Abstract from PubMed
Cell adhesion involved in signal transduction, tissue integrity and pathogen infection is mainly mediated by cell adhesion molecules (CAM). One CAM member, platelet-endothelial-cell adhesion molecule-1 (PECAM-1), plays an important role in tight junction among endothelia cells, leukocyte trafficking, and immune response through its homophilic and heterophilic binding patterns. Both kinds of interactions, which lead to endogenous and exogenous signal transmission, are derived from extracellular immunoglobulin-like (IgL) domains and cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) of PECAM-1. To date, the mechanism of trans-homophilic interaction of PECAM-1 remains unclear. Here, we present the crystal structure of PECAM-1 IgL1-2 trans-homo dimer. Both IgL 1 and 2 adopt the classical Ig domain conformation comprised of two layers of beta-sheets possessing antiparallel beta-strands with each being anchored by a pair of cysteines forming a disulfide bond. The dimer interface includes hydrophobic and hydrophilic interactions. The Small-Angle X-ray Scattering (SAXS) envelope of PECAM-1 IgL1-6 supported such a dimer formation in solution. Cell adhesion assays on wildtype and mutant PECAM-1 further characterized the structural determinants in cell junction and communication.
Structural Basis for Human PECAM-1-Mediated Trans-homophilic Cell Adhesion.,Hu M, Zhang H, Liu Q, Hao Q Sci Rep. 2016 Dec 13;6:38655. doi: 10.1038/srep38655. PMID:27958302[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Brown S, Heinisch I, Ross E, Shaw K, Buckley CD, Savill J. Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment. Nature. 2002 Jul 11;418(6894):200-3. PMID:12110892 doi:10.1038/nature00811
- ↑ Bergom C, Paddock C, Gao C, Holyst T, Newman DK, Newman PJ. An alternatively spliced isoform of PECAM-1 is expressed at high levels in human and murine tissues, and suggests a novel role for the C-terminus of PECAM-1 in cytoprotective signaling. J Cell Sci. 2008 Apr 15;121(Pt 8):1235-42. doi: 10.1242/jcs.025163. PMID:18388311 doi:10.1242/jcs.025163
- ↑ Dasgupta B, Dufour E, Mamdouh Z, Muller WA. A novel and critical role for tyrosine 663 in platelet endothelial cell adhesion molecule-1 trafficking and transendothelial migration. J Immunol. 2009 Apr 15;182(8):5041-51. doi: 10.4049/jimmunol.0803192. PMID:19342684 doi:10.4049/jimmunol.0803192
- ↑ Hu M, Zhang H, Liu Q, Hao Q. Structural Basis for Human PECAM-1-Mediated Trans-homophilic Cell Adhesion. Sci Rep. 2016 Dec 13;6:38655. doi: 10.1038/srep38655. PMID:27958302 doi:http://dx.doi.org/10.1038/srep38655
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