Fiche publication
Date publication
janvier 2016
Journal
eLife
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SPECHT Alexandre
Tous les auteurs :
Habermacher C, Martz A, Calimet N, Lemoine D, Peverini L, Specht A, Cecchini M, Grutter T
Lien Pubmed
Résumé
P2X receptors function by opening a transmembrane pore in response to extracellular ATP. Recent crystal structures solved in apo and ATP-bound states revealed molecular motions of the extracellular domain following agonist binding. However, the mechanism of pore opening still remains controversial. Here we use photo-switchable cross-linkers as 'molecular tweezers' to monitor a series of inter-residue distances in the transmembrane domain of the P2X2 receptor during activation. These experimentally based structural constraints combined with computational studies provide high-resolution models of the channel in the open and closed states. We show that the extent of the outer pore expansion is significantly reduced compared to the ATP-bound structure. Our data further reveal that the inner and outer ends of adjacent pore-lining helices come closer during opening, likely through a hinge-bending motion. These results provide new insight into the gating mechanism of P2X receptors and establish a versatile strategy applicable to other membrane proteins.
Mots clés
P2X receptors, azobenzene photoswitch, biophysics, gating mechanism, neuroscience, none, structural biology
Référence
Elife. 2016 Jan 25;5:e11050
