2LGX

NMR structure for Kindle-2 N-terminus

Summary for 2LGX

• Entry DOI: 10.2210/pdb2lgx/pdb
• NMR Information: BMRB: 17827
• Descriptor: Fermitin family homolog 2 (1 entity in total)
• Functional Keywords: kindlin, membrane, integrin activation, cell adhesion
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cell cortex: Q96AC1
• Total number of polymer chains: 1
• Total formula weight: 12987.99

Authors

Perera, H.D.,Ma, Y.,Yang, J.,Hirbawi, J.,Plow, E.F.,Qin, J. (deposition date: 2011-08-03, release date: 2011-11-30, Last modification date: 2024-05-15)

Primary citation

Perera, H.D.,Ma, Y.Q.,Yang, J.,Hirbawi, J.,Plow, E.F.,Qin, J.
Membrane Binding of the N-Terminal Ubiquitin-Like Domain of kindlin-2 Is Crucial for Its Regulation of Integrin Activation.
Structure, 19:1664-1671, 2011

PubMed Abstract: 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.

PubMed: 22078565
DOI: 10.1016/j.str.2011.08.012

Experimental method

SOLUTION NMR