Structure of the integral membrane domain of the GLP1 receptor.
A three-dimensional (3D) model of the integral membrane domain of the GLP1 receptor, a member of the secretin receptor family of the G-protein-coupled receptor superfamily is proposed. The probable arrangement of the seven helices in this receptor was deduced from a detailed analysis of all the sequences in the secretin receptor family. The analysis includes: 1) identifying the transmembrane helices, 2) charge distribution analysis to estimate to which extent the transmembrane helices are buried, 3) Fourier transform analysis of different property profiles within the transmembrane helices to determine the orientation of exposed and buried faces of the helices, 4) alignment of sequences with those of the rhodopsin-like family using the novel "cold spot" method reported herein, 5) determination of lengths of transmembrane helices and their connecting loops and the constraints these impose on packing, tilting and organization, 6) incorporation of mutagenesis and ligand specificity data. We find that there is a close similarity between the structural properties of receptors of the secretin family and those of the rhodopsin-like family as typified by the frog rhodopsin structure recently solved by electron cryomicroscopy.
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MedChem Research IV, Novo Nordisk Park, Novo Nordisk A/S, Måløv, Denmark.
Bywater
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D000595:Amino Acid Sequence; D017124:Conserved Sequence; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017433:Protein Structure, Secondary; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor