Mechanically unfolding proteins: the effect of unfolding history and the supramolecular scaffold.
The mechanical resistance of a folded domain in a polyprotein of five mutant I27 domains (C47S, C63S I27)(5)is shown to depend on the unfolding history of the protein. This observation can be understood on the basis of competition between two effects, that of the changing number of domains attempting to unfold, and the progressive increase in the compliance of the polyprotein as domains unfold. We present Monte Carlo simulations that show the effect and experimental data that verify these observations. The results are confirmed using an analytical model based on transition state theory. The model and simulations also predict that the mechanical resistance of a domain depends on the stiffness of the surrounding scaffold that holds the domain in vivo, and on the length of the unfolded domain. Together, these additional factors that influence the mechanical resistance of proteins have important consequences for our understanding of natural proteins that have evolved to withstand force.
Zinober
Rebecca C
RC
Department of Physics and Astronomy, University of Leeds, UK.
Brockwell
David J
DJ
Beddard
Godfrey S
GS
Blake
Anthony W
AW
Olmsted
Peter D
PD
Radford
Sheena E
SE
Smith
D Alastair
DA
D003198:Computer Simulation; D008958:Models, Molecular; D009010:Monte Carlo Method; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D011506:Proteins