Membrane binding of the N-terminal ubiquitin-like domain of kindlin-2 is crucial for its regulation of integrin activation. Structure 2011 Nov 09;19(11):1664-71
Date
11/15/2011Pubmed ID
22078565Pubmed Central ID
PMC3217186DOI
10.1016/j.str.2011.08.012Scopus ID
2-s2.0-80855133531 (requires institutional sign-in at Scopus site) 49 CitationsAbstract
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.
Author List
Perera HD, Ma YQ, Yang J, Hirbawi J, Plow EF, Qin JAuthor
Yan-Qing Ma PhD Associate Investigator in the Blood Research Institute department at BloodCenter of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceCell Membrane
Humans
Magnetic Resonance Spectroscopy
Membrane Proteins
Models, Molecular
Molecular Sequence Data
Neoplasm Proteins
Platelet Glycoprotein GPIIb-IIIa Complex
Protein Binding
Protein Structure, Tertiary
Protein Transport
Sequence Homology, Amino Acid
Surface Properties
Talin
