Conformational equilibrium of talin is regulated by anionic lipids

Xin Ye, Mark A. McLean, Stephen G. Sligar

Research output: Contribution to journalArticle

Abstract

A critical step in the activation of integrin receptors is the binding of talin to the cytoplasmic domain of the β subunits. This interaction leads to separation of the integrin α and β transmembrane domains and significant conformational changes in the extracellular domains, resulting in a dramatic increase in integrin's affinity for ligands. It has long been shown that the membrane bilayer also plays a critical role in the talin–integrin interaction. Anionic lipids are required for proper interaction, yet the specificity for specific anionic headgroups is not clear. In this report, we document talin–membrane interactions with bilayers of controlled composition using Nanodiscs and a FRET based binding and structural assay. We confirm that recruitment of the talin head domain to the membrane surface is governed by charge in the absence of other adapter proteins. In addition, measurement of the donor–acceptor distance is consistent with the hypothesis that anionic lipids promote a conformational change in the talin head domain allowing interaction of the F3 domain with the phospholipid bilayer. The magnitude of the F3 domain movement is altered by the identity of the phospholipid headgroup with phosphatidylinositides promoting the largest change. Our results suggest that phoshpatidylinositol-4,5-bisphosphate plays key a role in converting talin head domain to a conformation optimized for interactions with the bilayer and subsequently integrin cytoplasmic tails.

Original languageEnglish (US)
Pages (from-to)1833-1840
Number of pages8
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1858
Issue number8
DOIs
StatePublished - Aug 1 2016

Keywords

  • Conformational change
  • Lipid bilayer
  • Phosphatidylinositol
  • Phosphatidylserine
  • Talin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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