Crystal Structure of the PAC1R Extracellular Domain Unifies a Consensus Fold for Hormone Recognition by Class B G-Protein Coupled Receptors

Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR). Crystal structures of a number of Class B GPCR extracellular domains (ECD) bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology of the ECD and a distinct mode of ligand recognition. Here we report a 1.9 Å crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors

The barrier coastline of North Norfolk, with particular reference to Scolt Head Island

Situated on the barrier coastline of north Norfolk, eastern England, Scolt Head Island is remarkable for the long period—almost one hundred years—of sustained geo- morphological research, allowing a proper, and rare, assessment of the relative importance of the role of ‘normal’ processes versus extreme events (storm surge impacts) in determining landform evolution. Drawing on an extensive literature, the chapter reports on studies of the Holocene history of the barrier island and the historical dynamics of barrier westward extension and landward retreat (and associated sand dune initiation, growth and decline). It considers contemporary tidal channel hydrodynamics and patterns of back-barrier saltmarsh sedimentation and accretion. It concludes by considering how the process environment may change, and Scolt may develop, in the near future and the implications for landward ecosystems and communities