2V7D

14-3-3 protein zeta in complex with Thr758 phosphorylated integrin beta2 peptide

Summary for 2V7D

• Entry DOI: 10.2210/pdb2v7d/pdb
• Related: 1A37 1A38 1A4O
• Descriptor: 14-3-3 PROTEIN ZETA/DELTA, INTEGRIN BETA CHAIN, BETA 2 VARIANT (3 entities in total)
• Functional Keywords: membrane, integrin, receptor, cytoplasm, acetylation, transmembrane, beta2 integrin, phosphorylation, disease mutation, pyrrolidone carboxylic acid, 14-3-3 zeta, glycoprotein, cell adhesion, signaling protein
• Biological source: BOS TAURUS (BOVINE); More
• Cellular location: Cytoplasm: P63103
• Total number of polymer chains: 8
• Total formula weight: 116205.63

Authors

Takala, H.,Ylanne, J. (deposition date: 2007-07-30, release date: 2008-06-24, Last modification date: 2024-10-23)

Primary citation

Takala, H.,Nurminen, E.,Nurmi, S.M.,Aatonen, M.,Strandin, T.,Takatalo, M.,Kiema, T.,Gahmberg, C.G.,Ylanne, J.,Fagerholm, S.C.
Beta2 Integrin Phosphorylation on Thr758 Acts as a Molecular Switch to Regulate 14-3-3 and Filamin Binding.
Blood, 112:1853-, 2008

PubMed Abstract: 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 (K(d), 261 nM), whereas filamin bound only the unphosphorylated integrin cytoplasmic peptide (K(d), 0.5 mM). Phosphorylation did not regulate talin binding to beta2 directly, but 14-3-3 was able to outcompete 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.

PubMed: 18550856
DOI: 10.1182/BLOOD-2007-12-127795

Experimental method

X-RAY DIFFRACTION (2.5 Å)