title: A designed buried salt bridge modulates heterodimerization of a membrane peptide.
abstract: Specific helix-helix interactions underpin the correct assembly of multipass membrane proteins. Here, we show that a designed buried salt bridge mediates heterodimer formation of model transmembrane helical peptides in a pH-dependent manner. The model peptides bear side chains functionalized with either a carboxylic acid or a primary amine within a hydrophobic segment. The association behavior was monitored by Förster resonance energy transfer, revealing that heterodimer formation is maximized at a pH close to neutrality (pH 6.5), at which each peptide is found in a charged state. In contrast, heterodimerization is disfavored at low and high values of pH, because either the carboxylic acid or the primary amine is present in its neutral state, thus preventing the formation of a salt bridge. These findings provide a blueprint for the design and modulation of protein-protein interactions in membrane proteins.
authors.affiliation: Chemistry and Biochemistry, Arizona State University, Tempe, AZ.
authors.forename: Sandip
authors.initials: S
authors.lastname: Shinde
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Binder
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Goyal
authors.forename: B
authors.initials: B
authors.lastname: Woodrum
authors.forename: Sonia
authors.initials: S
authors.lastname: De Munari
authors.forename: Marcia
authors.initials: M
authors.lastname: Levitus
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ghirlanda
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D031541:Fluorescence Resonance Energy Transfer; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D012492:Salts / Q000737:chemistry*
chemical_list: D010455:Peptides; D012492:Salts
keywords: Förster resonance energy transfer; dimerization; heterodimer; membrane protein; micelles