Membrane binding of the N-terminal ubiquitin-like domain of kindlin-2 is crucial for its regulation of integrin activation

Structure. 2011 Nov 9;19(11):1664-71. doi: 10.1016/j.str.2011.08.012.


Kindlin-2 belongs to an emerging class of regulators for heterodimeric (α/β) integrin adhesion receptors. By binding to integrin β cytoplasmic tail via its C-terminal FERM-like domain, kindlin-2 promotes integrin activation. Intriguingly, this activation process depends on the N terminus of kindlin-2 (K2-N) that precedes the FERM domain. The molecular function of K2-N is unclear. We present the solution structure of K2-N, which displays a ubiquitin fold similar to that observed in kindlin-1. Using chemical shift mapping and mutagenesis, we found that K2-N contains a conserved positively charged surface that binds to membrane enriched with negatively charged phosphatidylinositol-(4,5)-bisphosphate. We show that while wild-type kindlin-2 is capable of promoting integrin activation, such ability is significantly reduced for its membrane-binding defective mutant. These data suggest a membrane-binding function of the ubiquitin-like domain of kindlin-2, which is likely common for all kindlins to promote their localization to the plasma membrane and control integrin activation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Cell Membrane / chemistry*
  • Humans
  • Magnetic Resonance Spectroscopy
  • Membrane Proteins / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry*
  • Platelet Glycoprotein GPIIb-IIIa Complex / chemistry*
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • Sequence Homology, Amino Acid
  • Surface Properties
  • Talin / chemistry


  • FERMT3 protein, human
  • Membrane Proteins
  • Neoplasm Proteins
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Talin

Associated data

  • PDB/2LGX