title: Pulling geometry defines the mechanical resistance of a beta-sheet protein.
abstract: Proteins show diverse responses when placed under mechanical stress. The molecular origins of their differing mechanical resistance are still unclear, although the orientation of secondary structural elements relative to the applied force vector is thought to have an important function. Here, by using a method of protein immobilization that allows force to be applied to the same all-beta protein, E2lip3, in two different directions, we show that the energy landscape for mechanical unfolding is markedly anisotropic. These results, in combination with molecular dynamics (MD) simulations, reveal that the unfolding pathway depends on the pulling geometry and is associated with unfolding forces that differ by an order of magnitude. Thus, the mechanical resistance of a protein is not dictated solely by amino acid sequence, topology or unfolding rate constant, but depends critically on the direction of the applied extension.
authors.affiliation: School of Biochemistry and Molecular Biology, University of Leeds, LS2 9JT, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Brockwell
authors.forename: Emanuele
authors.initials: E
authors.lastname: Paci
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Zinober
authors.forename: Godfrey S
authors.initials: GS
authors.lastname: Beddard
authors.forename: Peter D
authors.initials: PD
authors.lastname: Olmsted
authors.forename: D Alastair
authors.initials: DA
authors.lastname: Smith
authors.forename: Richard N
authors.initials: RN
authors.lastname: Perham
authors.forename: Sheena E
authors.initials: SE
authors.lastname: Radford
mesh_terms: D016880:Anisotropy; D004926:Escherichia coli / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D009010:Monte Carlo Method; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D012984:Software; D013696:Temperature; D013816:Thermodynamics
chemical_list: D011506:Proteins