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Mechanically unfolding proteins: The effect of unfolding history and the supramolecular scaffold
Author(s) -
Zinober Rebecca C.,
Brockwell David J.,
Beddard Godfrey S.,
Blake Anthony W.,
Olmsted Peter D.,
Radford Sheena E.,
Smith D. Alastair
Publication year - 2002
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.0224602
Subject(s) - scaffold , domain (mathematical analysis) , monte carlo method , stiffness , scaffold protein , protein engineering , protein domain , chemistry , biophysics , physics , computer science , biology , thermodynamics , biochemistry , mathematical analysis , statistics , mathematics , database , gene , enzyme , signal transduction
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.