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Mechanically Unfolding the Small, Topologically Simple Protein L

David J. Brockwell ^* , Godfrey S. Beddard  , Emanuele Paci  ^¶, Dan K. West ^* ¶, Peter D. Olmsted  ^¶, D. Alastair Smith  ^¶ and Sheena E. Radford ^* 

^* School of Biochemistry and Microbiology, Institute of Molecular Biophysics, School of Chemistry, Centre for Chemical Dynamics, and ^¶ School of Physics and Astronomy, University of Leeds, Leeds, United Kingdom

Correspondence: Address reprint requests to D. J. Brockwell or S. E. Radford, School of Biochemistry and Microbiology, University of Leeds. E-mails: brock{at}bmbaxp.leeds.ac.uk; s.e.radford{at}leeds.ac.uk.

ß-sheet proteins are generally more able to resist mechanical deformation than -helical proteins. Experiments measuring the mechanical resistance of ß-sheet proteins extended by their termini led to the hypothesis that parallel, directly hydrogen-bonded terminal ß-strands provide the greatest mechanical strength. Here we test this hypothesis by measuring the mechanical properties of protein L, a domain with a topology predicted to be mechanically strong, but with no known mechanical function. A pentamer of this small, topologically simple protein is resistant to mechanical deformation over a wide range of extension rates. Molecular dynamics simulations show the energy landscape for protein L is highly restricted for mechanical unfolding and that this protein unfolds by the shearing apart of two structural units in a mechanism similar to that proposed for ubiquitin, which belongs to the same structural class as protein L, but unfolds at a significantly higher force. These data suggest that the mechanism of mechanical unfolding is conserved in proteins within the same fold family and demonstrate that although the topology and presence of a hydrogen-bonded clamp are of central importance in determining mechanical strength, hydrophobic interactions also play an important role in modulating the mechanical resistance of these similar proteins.

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