Atomic force microscopy (AFM) imaging suggests that stromal interaction molecule 1 (STIM1) binds to Orai1 with sixfold symmetry

摘要

DepletionofCa2+fromtheendoplasmicreticulum(ER)lumentriggerstheopeningofCa2+release‐activatedCa2+(CRAC)channelsattheplasmamembrane.CRACchannelsareactivatedbystromalinteractionmolecule1(STIM1),anERresidentproteinthatsensesCa2+storedepletionandinteractswithOrai1,thepore‐formingsubunitofthechannel.ThesubunitstoichiometryoftheCRACchanneliscontroversial.Hereweprovideevidence,usingatomicforcemicroscopy(AFM)imaging,thatOrai1assemblesasahexamer,andthatSTIM1bindstoOrai1withsixfoldsymmetry.STIM1associateswithOrai1intheformofmonomers,dimers,andmultimericstring‐likestructuresthatformlinksbetweentheOrai1hexamers.OurresultsprovidenewinsightsintothenatureoftheinteractionsbetweenSTIM1andOrai1...