2v7d

14-3-3 PROTEIN ZETA IN COMPLEX WITH THR758 PHOSPHORYLATED INTEGRIN BETA2 PEPTIDE

spinqualitylabelsall models 2v7d, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2v7d is a 8 chain structure with sequence from Bovin. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: TPO Related: 1a37, 1a38, 1a4o Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Disease [ITB2_HUMAN] Defects in ITGB2 are the cause of leukocyte adhesion deficiency type 1 (LAD1) [MIM:116920]. LAD1 patients have recurrent bacterial infections and their leukocytes are deficient in a wide range of adhesion-dependent functions. Function [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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 14-3-3 protein

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