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Annular anionic lipids stabilize the integrin ?IIb?3 transmembrane complex.


ABSTRACT: 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 ?IIb?3 transmembrane (TM) complex is stabilized by a membrane-proximal ?IIb(Arg(995))-?3(Asp(723)) interaction; here, we examine the influence of anionic lipids on this complex. Anionic lipids compete for ?IIb(Arg(995)) contacts with ?3(Asp(723)) but paradoxically do not diminish the contribution of ?IIb(Arg(995))-?3(Asp(723)) to TM complex stability. Overall, anionic lipids in annular positions stabilize the ?IIb?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 on TM complex stability. We implicate changes in lipid headgroup accessibility to small molecules (physical membrane characteristics) and specific but dynamic protein-lipid contacts in this TM helix-helix stabilization. Thus, anionic lipids in ubiquitous annular positions can benefit the stability of membrane proteins while leaving membrane-proximal electrostatic interactions intact.

SUBMITTER: Schmidt T 

PROVIDER: S-EPMC4375483 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Annular anionic lipids stabilize the integrin αIIbβ3 transmembrane complex.

Schmidt Thomas T   Suk Jae-Eun JE   Ye Feng F   Situ Alan J AJ   Mazumder Parichita P   Ginsberg Mark H MH   Ulmer Tobias S TS  

The Journal of biological chemistry 20150129 13


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 αIIbβ3 transmembrane (TM) complex is stabilized by a membrane-proximal αIIb(Arg(995))-β3(Asp(723)) interaction; here, we examine the influence of anionic lipids on this complex. Anionic lipids compete fo  ...[more]

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