title: Wide turn diversity in protein transmembrane helices implications for G-protein-coupled receptor and other polytopic membrane protein structure and function.
abstract: Previously, we showed that perturbations of protein transmembrane helices are manifested as one of three types of noncanonical structures (wide turns, tight turns, and kinks), which, compared with alpha-helices, are evident by distinctive Calpha(i)-->Calpha(x) distances. In this study, we report the analysis of more than 3000 transmembrane helices in 244 crystal structures from which we identified 70 wide turns (29 proline- and 41 nonproline-induced). Based on differences in the Calpha(i)-->Calpha(i)(-4) and Calpha(i)-->Calpha(i)(-5) profiles, we show that wide turns can be subclassified into three distinct subclasses (W(1), W(2), and W(3)) that differ with regard to the number and position of backbone i --> i-5 H-bonds formed N-terminal to the perturbing or signature proline or nonproline residue. Although wide turns generally produce changes in helical direction of 20 degrees to 30 degrees and a lateral shift in the helical axis, some of the W(3) subclass are associated with changes of <5 degrees . We also show that the distinct architectural features of wide turns allow the carbonyl bond of the i-4th residue, which is located on the widened loop of a wide turn, to be directed away from the helical axis. This provides regions of flexibility within helical regions allowing, for example, unique opportunities for interhelical H-bonding, including interactions with glycine zipper motifs, and for ion and cofactor binding. Furthermore, differences in wide-turn subtype usage by related protein family members, such as the G-protein-coupled receptors rhodopsin and the beta2-adrenergic receptor, can significantly affect the orientation and position of residues critical for ligand binding and receptor activation.
authors.affiliation: Computational and Structural Biology Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
authors.forename: R Peter
authors.initials: RP
authors.lastname: Riek
authors.forename: Angela A
authors.initials: AA
authors.lastname: Finch
authors.forename: Gillian E
authors.initials: GE
authors.lastname: Begg
authors.forename: Robert M
authors.initials: RM
authors.lastname: Graham
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D006860:Hydrogen Bonding; D045342:Light-Harvesting Protein Complexes / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010084:Oxidation-Reduction; D011392:Proline; D017433:Protein Structure, Secondary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D045342:Light-Harvesting Protein Complexes; D008565:Membrane Proteins; C088749:PufX protein, Rhodobacter; D043562:Receptors, G-Protein-Coupled; D011392:Proline