title: Complex interactions at the helix-helix interface stabilize the glycophorin A transmembrane dimer.
abstract: To explore the residue interactions in the glycophorin A dimerization motif, an alanine scan double mutant analysis at the helix-helix interface was carried out. These data reveal a combination of additive and coupled effects. The majority of the double mutants are found to be equally or slightly more stable than would be predicted by the sum of the energetic cost of the single-point mutants. The proximity of the mutated sites is not related to the presence of coupling between those sites. Previous studies reveal that a single face of the glycophorin A monomer contains a specific glycine-containing motif (GxxxG) that is thought to be a driving force for the association of transmembrane helices. Double mutant cycles suggest that the relationship of the GxxxG motif to the remainder of the helix-helix interface is complex. Sequences containing mutations that abolish the GxxxG motif retain an ability to dimerize, while a sequence containing a GxxxG motif appears unable to form dimers. The energetic effects of weakly coupled and additive double mutants can be explained by changes in van der Waals interactions at the dimer interface. These results emphasize the fact that the sequence context of the dimer interface modulates the strength of the glycophorin A GxxxG-mediated transmembrane dimerization reaction.
authors.affiliation: T.C. Jenkins Department of Biophysics, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
authors.forename: Abigail K
authors.initials: AK
authors.lastname: Doura
authors.forename: Karen G
authors.initials: KG
authors.lastname: Fleming
mesh_terms: D020816:Amino Acid Motifs; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D006021:Glycophorins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009154:Mutation; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D006021:Glycophorins