title: Lipid solvation effects contribute to the affinity of Gly-xxx-Gly motif-mediated helix-helix interactions.
abstract: Interactions between transmembrane helices are mediated by the concave Gly-xxx-Gly motif surface. Whether Gly residues per se are sufficient for selection of this motif has not been established. Here, we used the in vivo TOXCAT assay to measure the relative affinities of all 18 combinations of Gly, Ala, and Ser "small-xxx-small" mutations in glycophorin A (GpA) and bacteriophage M13 major coat protein (MCP) homodimers. Affinity values were compared with the accessibility to a methylene-sized probe of the total surface area of each helix monomer as a measure of solvation by membrane components. A strong inverse correlation was found between nonpolar-group lipid accessibility and dimer affinity (R = 0.75 for GpA, p = 0.013, and R = 0.81 for MCP, p = 0.004), suggesting that lipid as a poor membrane protein solvent, conceptually analogous to water in soluble protein folding, can contribute to dimer stability and help to define helix-helix interfaces.
authors.affiliation: Division of Structural Biology and Biochemistry, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Johnson
authors.forename: Arianna
authors.initials: A
authors.lastname: Rath
authors.forename: Roman A
authors.initials: RA
authors.lastname: Melnyk
authors.forename: Charles M
authors.initials: CM
authors.lastname: Deber
mesh_terms: D000409:Alanine / Q000737:chemistry; D020816:Amino Acid Motifs / Q000235:genetics; D019943:Amino Acid Substitution; D017104:Bacteriophage M13 / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry*; D019281:Dimerization; D005998:Glycine / Q000737:chemistry*; D006021:Glycophorins / Q000737:chemistry* / Q000235:genetics; D008055:Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012694:Serine / Q000737:chemistry; D012995:Solubility; D014758:Viral Core Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D006021:Glycophorins; D008055:Lipids; D014758:Viral Core Proteins; D012694:Serine; D000409:Alanine; D005998:Glycine