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Unfolding dynamics of proteins under applied force

Smith, D.A., Brockwell, D.J., Zinober, R.C., Blake, A.W., Beddard, G.S., Olmsted, P.D. and Radford, S.E. (2003) Unfolding dynamics of proteins under applied force. Philosophical Transactions Of The Royal Society Of London Series A - Mathematical Physical and Engineering Sciences, 361 (1805). 713 -730. ISSN 1471-2962

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Understanding the mechanisms of protein folding is a major challenge that is being addressed effectively by collaboration between researchers in the physical and life sciences. Recently, it has become possible to mechanically unfold proteins by pulling on their two termini using local force probes such as the atomic force microscope. Here, we present data from experiments in which synthetic protein polymers designed to mimic naturally occurring polyproteins have been mechanically unfolded. For many years protein folding dynamics have been studied using chemical denaturation, and we therefore firstly discuss our mechanical unfolding data in the context of such experiments and show that the two unfolding mechanisms are not the same, at least for the proteins studied here. We also report unexpected observations that indicate a history effect in the observed unfolding forces of polymeric proteins and explain this in terms of the changing number of domains remaining to unfold and the increasing compliance of the lengthening unstructured polypeptide chain produced each time a domain unfolds.

Item Type: Article
Copyright, Publisher and Additional Information: Copyright © 2003 The Royal Society
Keywords: protein folding, atomic force microscope, mechanical unfolding, force, single molecule, mechanical resistance
Institution: The University of Leeds
Academic Units: The University of Leeds > Faculty of Maths and Physical Sciences (Leeds) > School of Physics and Astronomy (Leeds)
The University of Leeds > Faculty of Maths and Physical Sciences (Leeds) > School of Chemistry (Leeds)
The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds)
Depositing User: Repository Officer
Date Deposited: 13 Mar 2006
Last Modified: 18 Aug 2015 02:26
Published Version: http://www.journals.royalsoc.ac.uk/link.asp?id=b62...
Status: Published
Refereed: Yes
Identification Number: 10.1098/rsta.2002.1160
URI: http://eprints.whiterose.ac.uk/id/eprint/609

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