title: Unifying family A GPCR theories of activation.
abstract: Several new pairs of active and inactive GPCR structures have recently been solved enabling detailed structural insight into the activation process, not only of rhodopsin but now also of the β2 adrenergic, M2 muscarinic and adenosine A2A receptors. Combined with structural analyses they have enabled us to examine the different recent theories proposed for GPCR activation and show that they are all indeed parts of the same process, and are intrinsically related through their effect on the central hydrophobic core of GPCRs. This new unifying general process of activation is consistent with the identification of known constitutively active mutants and an in-depth conservational analysis of significant residues implicated in the process.
authors.affiliation: Heptares Therapeutics BioPark, Broadwater Road, Welwyn Garden City AL7 3AX United Kingdom. Electronic address: ben.tehan@heptares.com.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Tehan
authors.affiliation: Heptares Therapeutics BioPark, Broadwater Road, Welwyn Garden City AL7 3AX United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bortolato
authors.affiliation: Heptares Therapeutics BioPark, Broadwater Road, Welwyn Garden City AL7 3AX United Kingdom.
authors.forename: Frank E
authors.initials: FE
authors.lastname: Blaney
authors.affiliation: Heptares Therapeutics BioPark, Broadwater Road, Welwyn Garden City AL7 3AX United Kingdom.
authors.forename: Malcolm P
authors.initials: MP
authors.lastname: Weir
authors.affiliation: Heptares Therapeutics BioPark, Broadwater Road, Welwyn Garden City AL7 3AX United Kingdom.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Mason
mesh_terms: D000818:Animals; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D043562:Receptors, G-Protein-Coupled
keywords: Activation; Conservational analysis; Constitutive activity; GPCR