title: Solvent-Exposed Salt Bridges Influence the Kinetics of α-Helix Folding and Unfolding.
abstract: Salt bridges are known to play an essential role in the thermodynamic stability of the folded conformation of many proteins, but their influence on thekineticsof folding remains largely unknown. Here, we investigate the effect of Glu-Arg salt bridges on the kinetics of α-helix folding using temperature-jump transient-infrared spectroscopy and steady-state UV circular dichroism. We find that geometrically optimized salt bridges (Glu-and Arg+are spaced four peptide units apart, and the Glu/Arg order is such that the side-chain rotameric preferences favor salt-bridge formation) significantly speed up folding and slow down unfolding, whereas salt bridges with unfavorable geometry slow down folding and slightly speed up unfolding. Our observations suggest a possible explanation for the surprising fact that many biologically active proteins contain salt bridges that do not stabilize the native conformation: these salt bridges might have a kinetic rather than a thermodynamic function.
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam , Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Heleen
authors.initials: H
authors.lastname: Meuzelaar
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam , Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Tros
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam , Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Adriana
authors.initials: A
authors.lastname: Huerta-Viga
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam , Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Chris N
authors.initials: CN
authors.lastname: van Dijk
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam , Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Vreede
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam , Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Woutersen