Annular Anionic Lipids Stabilize the Integrin alpha IIb beta 3 Transmembrane Complex

作者：Schmidt Thomas; Suk Jae Eun; Ye Feng; Situ Alan J; Mazumder Parichita; Gin**erg Mark H; Ulmer Tobias S^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2015, 290(13): 8283-8293.

DOI：10.1074/jbc.M114.623504

Cationic membrane-proximal amino acids determine the topology of membrane proteins by interacting with anionic lipids that are restricted to the intracellular membrane leaflet. This mechanism implies that anionic lipids interfere with electrostatic interactions of membrane proteins. The integrin alpha IIb beta 3 transmembrane (TM) complex is stabilized by a membraneproximal alpha IIb(Arg(995))-alpha 3(Asp(723)) interaction; here, we examine the influence of anionic lipids on this complex. Anionic lipids compete for alpha IIb(Arg(995)) contacts with beta 3(Asp(723)) but paradoxically do not diminish the contribution of alpha IIb(Arg(995))-beta 3(Asp(723)) to TM complex stability. Overall, anionic lipids in annular positions stabilize the similar to IIb similar to 3 TM complex by up to 0.50 +/- 0.02 kcal/mol relative to zwitterionic lipids in a headgroup structure-dependent manner. Comparatively, integrin receptor activation requires TM complex destabilization of 1.5 +/- 0.2 kcal/mol, revealing a sizeable influence of lipid composition onTMcomplex stability. Weimplicate changes in lipid headgroup accessibility to small molecules (physical membrane characteristics) and specific but dynamic protein-lipid contacts in thisTMhelix-helix stabilization. Thus, anionic lipids in ubiquitous annular positions can benefit the stability of membrane proteins while leaving membrane-proximal electrostatic interactions intact.

• 出版日期2015-3-27