2H7E

Solution structure of the talin F3 domain in complex with a chimeric beta3 integrin-PIP kinase peptide- minimized average structure

Summary for 2H7E

• Entry DOI: 10.2210/pdb2h7e/pdb
• Related: 2H7D
• NMR Information: BMRB: 7150
• Descriptor: Talin-1, Chimera of 24-mer peptide from Integrin beta-3 and 10-mer peptide from Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma (2 entities in total)
• Functional Keywords: protein-peptide complex, alpha helix, beta sheet, structural protein
• Biological source: Gallus gallus (chicken); More
• Cellular location: Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side: P54939; Endomembrane system: O70161
• Total number of polymer chains: 2
• Total formula weight: 15755.15

Authors

Wegener, K.L. (deposition date: 2006-06-02, release date: 2007-01-30, Last modification date: 2024-11-06)

Primary citation

Wegener, K.L.,Partridge, A.W.,Han, J.,Pickford, A.R.,Liddington, R.C.,Ginsberg, M.H.,Campbell, I.D.
Structural basis of integrin activation by talin
CELL(CAMBRIDGE,MASS.), 128:171-182, 2007

PubMed Abstract: Regulation of integrin affinity (activation) is essential for metazoan development and for many pathological processes. Binding of the talin phosphotyrosine-binding (PTB) domain to integrin beta subunit cytoplasmic domains (tails) causes activation, whereas numerous other PTB-domain-containing proteins bind integrins without activating them. Here we define the structure of a complex between talin and the membrane-proximal integrin beta3 cytoplasmic domain and identify specific contacts between talin and the integrin tail required for activation. We used structure-based mutagenesis to engineer talin and beta3 variants that interact with comparable affinity to the wild-type proteins but inhibit integrin activation by competing with endogenous talin. These results reveal the structural basis of talin's unique ability to activate integrins, identify an interaction that could aid in the design of therapeutics to block integrin activation, and enable engineering of cells with defects in the activation of multiple classes of integrins.

PubMed: 17218263
DOI: 10.1016/j.cell.2006.10.048

Experimental method

SOLUTION NMR