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| | <StructureSection load='2v7d' size='340' side='right'caption='[[2v7d]], [[Resolution|resolution]] 2.50Å' scene=''> | | <StructureSection load='2v7d' size='340' side='right'caption='[[2v7d]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2v7d]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Bovin Bovin]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V7D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2v7d]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V7D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V7D FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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]] 2.5Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1a37|1a37]], [[1a38|1a38]], [[1a4o|1a4o]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</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=2v7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v7d OCA], [https://pdbe.org/2v7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v7d RCSB], [https://www.ebi.ac.uk/pdbsum/2v7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v7d 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=2v7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v7d OCA], [https://pdbe.org/2v7d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v7d RCSB], [https://www.ebi.ac.uk/pdbsum/2v7d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v7d ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[https://www.uniprot.org/uniprot/ITB2_HUMAN ITB2_HUMAN]] Defects in ITGB2 are the cause of leukocyte adhesion deficiency type 1 (LAD1) [MIM:[https://omim.org/entry/116920 116920]]. LAD1 patients have recurrent bacterial infections and their leukocytes are deficient in a wide range of adhesion-dependent functions.<ref>PMID:7509236</ref> <ref>PMID:1346613</ref> <ref>PMID:1968911</ref> <ref>PMID:1694220</ref> <ref>PMID:1590804</ref> <ref>PMID:1352501</ref> <ref>PMID:1347532</ref> <ref>PMID:7686755</ref> <ref>PMID:9884339</ref> <ref>PMID:20529581</ref> <ref>PMID:20549317</ref> | |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ITB2_HUMAN ITB2_HUMAN]] Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrins alpha-M/beta-2 and alpha-X/beta-2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin alpha-X/beta-2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin alpha-M/beta-2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin alpha-M/beta-2 is also a receptor for factor X. Integrin alpha-D/beta-2 is a receptor for ICAM3 and VCAM1. Triggers neutrophil transmigration during lung injury through PTK2B/PYK2-mediated activation.<ref>PMID:18587400</ref>
| + | [https://www.uniprot.org/uniprot/1433Z_BOVIN 1433Z_BOVIN] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Activates the ADP-ribosyltransferase (exoS) activity of bacterial origin.<ref>PMID:7931346</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Takala, H]] | + | [[Category: Takala H]] |
| - | [[Category: Ylanne, J]] | + | [[Category: Ylanne J]] |
| - | [[Category: 14-3-3 zeta]]
| + | |
| - | [[Category: Acetylation]]
| + | |
| - | [[Category: Beta2 integrin]]
| + | |
| - | [[Category: Cell adhesion]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Integrin]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Phosphorylation]]
| + | |
| - | [[Category: Pyrrolidone carboxylic acid]]
| + | |
| - | [[Category: Receptor]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Function
1433Z_BOVIN Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Activates the ADP-ribosyltransferase (exoS) activity of bacterial origin.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Leukocyte integrins of the beta2 family are essential for immune cell-cell adhesion. In activated cells, beta2 integrins are phosphorylated on the cytoplasmic Thr758, leading to 14-3-3 protein recruitment to the beta2 integrin. The mutation of this phosphorylation site impairs cell adhesion, actin reorganization and cell spreading. Thr758 is contained in a Thr-triplet of beta2 that also mediates binding to filamin. Here, we investigated the binding of filamin, talin and 14-3-3 proteins to phosphorylated and unphosphorylated beta2 integrins by biochemical methods and X-ray crystallography. 14-3-3 proteins bound only to the phosphorylated integrin cytoplasmic peptide, with a high affinity (Kd 261 nM), whereas filamin bound only the unphosphorylated integrin cytoplasmic peptide (Kd 0.5 mM). Phosphorylation did not regulate talin binding to beta2 directly, but 14-3-3 was able to out-compete talin for the binding to phosphorylated beta2-integrin. X-ray crystallographic data clearly explained how phosphorylation eliminated filamin binding and induced 14-3-3 protein binding. Filamin knockdown in T cells led to an increase in stimulated cell adhesion to ICAM-1-coated surfaces. Our results suggest that the phosphorylation of beta2 integrins on Thr758 acts as a molecular switch to inhibit filamin binding and allow 14-3-3 protein binding to the integrin cytoplasmic domain, thereby modulating T cell adhesion.
Integrin {beta}2 phosphorylation on THR758 acts as a molecular switch to regulate 14-3-3 and filamin binding.,Takala H, Nurminen E, Nurmi SM, Aatonen M, Strandin T, Takatalo M, Kiema T, Gahmberg CG, Ylanne J, Fagerholm SC Blood. 2008 Jun 12;. PMID:18550856[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Tanji M, Horwitz R, Rosenfeld G, Waymire JC. Activation of protein kinase C by purified bovine brain 14-3-3: comparison with tyrosine hydroxylase activation. J Neurochem. 1994 Nov;63(5):1908-16. PMID:7931346
- ↑ Takala H, Nurminen E, Nurmi SM, Aatonen M, Strandin T, Takatalo M, Kiema T, Gahmberg CG, Ylanne J, Fagerholm SC. Integrin {beta}2 phosphorylation on THR758 acts as a molecular switch to regulate 14-3-3 and filamin binding. Blood. 2008 Jun 12;. PMID:18550856 doi:blood-2007-12-127795
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