Spatial coordination of kindlin-2 with talin head domain in interaction with integrin β cytoplasmic tails.
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.
Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology/NB-50, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Kamila
K
Bledzka
Jianmin
J
Liu
Zhen
Z
Xu
H Dhanuja
HD
Perera
Satya P
SP
Yadav
Katarzyna
K
Bialkowska
Jun
J
Qin
Yan-Qing
YQ
Ma
Edward F
EF
Plow
D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002151:Calorimetry; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism*; D039641:Integrin beta Chains / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D020349:Surface Plasmon Resonance; D016608:Talin / Q000737:chemistry* / Q000378:metabolism*
C477322:FERMT3 protein, human; D039641:Integrin beta Chains; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016608:Talin