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Spatial coordination of kindlin-2 with talin head domain in interaction with integrin β cytoplasmic tails. J Biol Chem 2012 Jul 13;287(29):24585-94

Date

06/01/2012

Pubmed ID

22648415

Pubmed Central ID

PMC3397883

DOI

10.1074/jbc.M111.336743

Scopus ID

2-s2.0-84863793892 (requires institutional sign-in at Scopus site)   71 Citations

Abstract

Both talin head domain and kindlin-2 interact with integrin β cytoplasmic tails, and they function in concert to induce integrin activation. Binding of talin head domain to β cytoplasmic tails has been characterized extensively, but information on the interaction of kindin-2 with this integrin segment is limited. In this study, we systematically examine the interactions of kindlin-2 with integrin β tails. Kindlin-2 interacted well with β(1) and β(3) tails but poorly with the β(2) cytoplasmic tail. This binding selectivity was determined by the non-conserved residues, primarily the three amino acids at the extreme C terminus of the β(3) tail, and the sequence in β(2) was non-permissive. The region at the C termini of integrin β(1) and β(3) tails recognized by kindlin-2 was a binding core of 12 amino acids. Kindlin-2 and talin head do not interact with one another but can bind simultaneously to the integrin β(3) tail without enhancing or inhibiting the interaction of the other binding partner. Kindlin-2 itself failed to directly unclasp integrin α/β tail complex, indicating that kindlin-2 must cooperate with talin to support the integrin activation mechanism.

Author List

Bledzka K, Liu J, Xu Z, Perera HD, Yadav SP, Bialkowska K, Qin J, Ma YQ, Plow EF

Author

Yan-Qing Ma PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
CHO Cells
Calorimetry
Chromatography, High Pressure Liquid
Cricetinae
Cytoplasm
Integrin beta Chains
Magnetic Resonance Spectroscopy
Membrane Proteins
Neoplasm Proteins
Protein Structure, Tertiary
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Surface Plasmon Resonance
Talin