Prediction of the translocation kinetics of a protein from
its mechanical properties
Daniel K West 1, David J Brockwell 1 and Emanuele Paci 1*
1 University of Leeds
* To whom correspondence should be addressed. E-mail: e.paci{at}leeds.ac.uk.
Submitted on May 18, 2006
Revised on May 31, 2006
Accepted on 16 June 2006
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Abstract |
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Proteins are actively unfolded in order to pass through narrow channels in macromolecular complexes that catalyse protein translocation and degradation. Catalysed unfolding shares many features that characterise the mechanical unfolding of proteins using the atomic force microscope (AFM). However, simulations of unfolding induced by the AFM and when a protein is translocated through a pore suggest that each process occurs by distinct pathways. The link, if any, between each type of unfolding therefore, is not known. We show that the mechanical unfolding energy landscape of a protein, obtained using an atomistic molecular model, can be used to predict both the relative mechanical strength of proteins when unfolded using the AFM and when unfolded by translocation into a pore. We thus link the two processes and show that the import rate through a pore not only depends on the location of the initiation tag but also on the mechanical properties of the protein when averaged
over all the possible geometries which are relevant for a given translocation initiation site.
Key Words:
atomic force microscopy, coarse-grained models, mechanical unfolding, molecular dynamics, protein translocation and degradation, protein unfolding
