Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

To elucidate the kinetic importance of structural intermediates in single-domain proteins, we measured the effect of solution conditions and amino-acid changes at a central core residue of ubiquitin (Val 26) on the kinetics of folding and unfolding. Kinetic analysis in terms of a sequential three-state mechanism provides insight into the contribution of specific interactions within the ubiquitin core to the structural stability of the native and intermediate states. The observations that disruptive mutations and/or addition of denaturants result in an apparent two-state folding process with slower rates is explained by the destabilization of a partially folded intermediate, which is in rapid equilibrium with unfolded states. The model predicts that under sufficiently stabilizing conditions kinetic intermediates may become populated even for proteins showing apparent two-state kinetics.

Original publication

DOI

10.1038/nsb0296-193

Type

Journal article

Journal

Nature structural biology

Publication Date

02/1996

Volume

3

Pages

193 - 205

Addresses

Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.

Keywords

Humans, Valine, Ubiquitins, Spectrometry, Fluorescence, Protein Denaturation, Protein Folding, Kinetics, Mutation, Models, Chemical, Models, Molecular