title: pH-triggered strand exchange in coiled-coil heterotrimers.
abstract: The capacity for pH-triggered strand exchange in designed coiled-coil heterotrimers is demonstrated. Systems employing both hydrophobic core (steric matching) and hydrophilic interface (electrostatic matching) design principles assemble into specific 1:1:1 heterotrimers. Alteration of pH creates electrostatic mismatches, inducing strand exchange in the presence of a suitable replacement peptide. Complexes with one Lys/Lys interface, favored at neutral to high pH, can be transformed to ones with a Glu/Glu contact by lowering pH and adding an appropriate new binding partner. The need to simultaneously maintain matched core alignments enforces specificity in this exchange, such that only a single specific peptide is replaced. These principles have subsequently been applied to the design of dynamically triggered cross-linked structures, in which a bifunctional disulfide-tethered peptide can cross-link two heterotrimers. Both formation and disruption of the cross-link are under pH control.
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Schnarr
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Kennan
mesh_terms: D000595:Amino Acid Sequence; D003432:Cross-Linking Reagents / Q000737:chemistry; D018698:Glutamic Acid / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008239:Lysine / Q000737:chemistry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
chemical_list: D003432:Cross-Linking Reagents; D011506:Proteins; D018698:Glutamic Acid; D008239:Lysine