Structural and thermodynamic basis of proline-induced transmembrane complex stabilization.

ABSTRACT: In membrane proteins, proline-mediated helix kinks are indispensable for the tight packing of transmembrane (TM) helices. However, kinks invariably affect numerous interhelical interactions, questioning the acceptance of proline substitutions and evolutionary origin of kinks. Here, we present the structural and thermodynamic basis of proline-induced integrin ?IIb?3 TM complex stabilization to understand the introduction of proline kinks in membrane proteins. In phospholipid bicelles, the A711P substitution in the center of the ?3 TM helix changes the direction of adjacent helix segments to form a 35?±?2° angle and predominantly repacks the segment in the inner membrane leaflet due to a swivel movement. This swivel repacks hydrophobic and electrostatic interhelical contacts within intracellular lipids, resulting in an overall TM complex stabilization of -0.82?±?0.01?kcal/mol. Thus, proline substitutions can directly stabilize membrane proteins and such substitutions are proposed to follow the structural template of integrin ?IIb?3(A711P).

SUBMITTER: Schmidt T 

PROVIDER: S-EPMC4951694 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature