2v7d
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | + | ==14-3-3 PROTEIN ZETA IN COMPLEX WITH THR758 PHOSPHORYLATED INTEGRIN BETA2 PEPTIDE== | |
| - | + | <StructureSection load='2v7d' size='340' side='right' caption='[[2v7d]], [[Resolution|resolution]] 2.50Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[2v7d]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2V7D FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | ||
| + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a37|1a37]], [[1a38|1a38]], [[1a4o|1a4o]]</td></tr> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2v7d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v7d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2v7d RCSB], [http://www.ebi.ac.uk/pdbsum/2v7d PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/ITB2_HUMAN ITB2_HUMAN]] Defects in ITGB2 are the cause of leukocyte adhesion deficiency type 1 (LAD1) [MIM:[http://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 == | ||
| + | [[http://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> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v7/2v7d_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:18550856</ref> | |
| - | + | ||
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | == | + | ==See Also== |
| - | [[ | + | *[[14-3-3 protein|14-3-3 protein]] |
| - | + | == References == | |
| - | == | + | <references/> |
| - | + | __TOC__ | |
| + | </StructureSection> | ||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: Takala, H.]] | [[Category: Takala, H.]] | ||
Revision as of 02:08, 1 October 2014
14-3-3 PROTEIN ZETA IN COMPLEX WITH THR758 PHOSPHORYLATED INTEGRIN BETA2 PEPTIDE
| |||||||||||
