Chapter 30. Three-dimensional Models of G-Protein Coupled Receptors

摘要: Publisher Summary The cloning and sequencing of the G-protein coupled receptors (GPCRs) has revealed a superfamily GPCR proteins that activate various guanine-nucleotide binding (G) proteins. Throughout this chapter, distinction is made among GPCRs on basis chemical nature their ligands. Bacteriorhodopsin (BR), major light-sensitive protein purple membrane Halobacterium halobium , been first bound found to be organized into seven transmembrane spanning domains. Although BR not GPCR, sensory require an intermediary called transducin second messenger system. To identify hydrophobic segments in primary sequences, theoretical methods, such as hydrophobicity profiles, moments, helix amphiphilicity, secondary structure prediction can applied. N-terminal segment length varies extreme across families. Protein chemistry experiments have identified N-glycosylation sites. intracellular loops C-terminal fragments shown affect signal transduction through coupling G-protein. all GPCRs, they are characterized by heavy content basic amino acid residues. A number recently proposed structural models for non-peptide suggest schematic 2-dimensional (2D) representations, 3D limited selected helices or highly refined sometimes incorporate connecting loops. Very few modeling reports expanded include challenge loop modeling. internal proline residues impose curving effect helices, molding domains overall oblong shape. It long speculated receptor conformational change, triggered agonist binding, would responsible initiating resulting mechanism. Variations familiar theme reported very peptide receptors.