Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds
Resource
Proc. Natl. Acad. Sci. U. S. A., 110(13), 5022-5027
Journal
Proceedings of the National Academy of Sciences
Pages
5022-5027
Date Issued
2013
Date
2013
Author(s)
Lee, Cho-yin
Lou, Jizhong
Wen, Kuo-kuang
McKane, Melissa
Eskin, Suzanne G.
Ono, Shoichiro
Chien, Shu
Rubenstein, Peter A.
Zhu, Cheng
McIntire, Larry V.
Abstract
As a key element in the cytoskeleton, actin filaments are highly dynamic structures that constantly sustain forces. However, the fundamental question of how force regulates actin dynamics is unclear. Using atomic force microscopy force-clamp experiments, we show that tensile force regulates G-actin/G-actin and G-actin/F-actin dissociation kinetics by prolonging bond lifetimes (catch bonds) at a low force range and by shortening bond lifetimes (slip bonds) beyond a threshold. Steered molecular dynamics simulations reveal force-induced formation of new interactions that include a lysine 113(K113):glutamic acid 195 (E195) salt bridge between actin subunits, thus suggesting a molecular basis for actin catch-slip bonds. This structural mechanism is supported by the suppression of the catch bonds by the single-residue replacements K113 to serine (K113S) and E195 to serine (E195S) on yeast actin. These results demonstrate and provide a structural explanation for actin catch-slip bonds, which may provide a mechanoregulatory mechanism to control cell functions by regulating the depolymerization kinetics of force-bearing actin filaments throughout the cytoskeleton.
Subjects
single-molecule force spectroscopy
mechanotransduction
mechanosensing
nemaline myopathy