Conformational restriction of G‐proteins Coupled Receptors (GPCRs) upon complexation to G‐proteins: A putative activation mode of GPCRs?

摘要

GPCRsundergolargeconformationalchangesduringtheiractivation.StartingfromexistingX‐raystructures,weusedNormalModesAnalysestostudythecollectivemotionsoftheagonist‐boundβ2‐adrenergicreceptorbothinitsisolated“uncoupled”andG‐protein“coupled”conformations.Weinterestinglyobservedthatthereceptorwasabletoadoptonlyonemajormotionintheprotein:proteincomplex.Thismotioncorrespondedtoananti‐symmetricrotationofbothitsextra‐andintra‐cellularparts,withakeyroleofpreviouslyidentifiedhighlyconservedprolineresidues.BecausethismotionwasalsoretrievedwhenperformingNMAon7otherGPCRswhichstructureswereavailable,itisstronglysuspectedtopossessasignificantbiologicalrole,possiblybeingthe“activationmode”ofaGPCRwhencoupledtoG‐proteins...