title: Conformational dynamics of activation for the pentameric complex of dimeric G protein-coupled receptor and heterotrimeric G protein.
abstract: Photoactivation of rhodopsin (Rho), a G protein-coupled receptor, causes conformational changes that provide a specific binding site for the rod G protein, G(t). In this work we employed structural mass spectrometry techniques to elucidate the structural changes accompanying transition of ground state Rho to photoactivated Rho (Rho(∗)) and in the pentameric complex between dimeric Rho(∗) and heterotrimeric G(t). Observed differences in hydroxyl radical labeling and deuterium uptake between Rho(∗) and the (Rho(∗))(2)-G(t) complex suggest that photoactivation causes structural relaxation of Rho following its initial tightening upon G(t) coupling. In contrast, nucleotide-free G(t) in the complex is significantly more accessible to deuterium uptake allowing it to accept GTP and mediating complex dissociation. Thus, we provide direct evidence that in the critical step of signal amplification, Rho(∗) and G(t) exhibit dissimilar conformational changes when they are coupled in the (Rho(∗))(2)-G(t) complex.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106-4988, USA.
authors.forename: Tivadar
authors.initials: T
authors.lastname: Orban
authors.forename: Beata
authors.initials: B
authors.lastname: Jastrzebska
authors.forename: Sayan
authors.initials: S
authors.lastname: Gupta
authors.forename: Benlian
authors.initials: B
authors.lastname: Wang
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyagi
authors.forename: Mark R
authors.initials: MR
authors.lastname: Chance
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry*; D008027:Light; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin; D020962:Heterotrimeric GTP-Binding Proteins