title: Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds.
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.
authors: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors: Cho-yin
authors: CY
authors: Lee
authors: Jizhong
authors: J
authors: Lou
authors: Kuo-kuang
authors: KK
authors: Wen
authors: Melissa
authors: M
authors: McKane
authors: Suzanne G
authors: SG
authors: Eskin
authors: Shoichiro
authors: S
authors: Ono
authors: Shu
authors: S
authors: Chien
authors: Peter A
authors: PA
authors: Rubenstein
authors: Cheng
authors: C
authors: Zhu
authors: Larry V
authors: LV
authors: McIntire
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D000199:Actins / Q000737:chemistry* / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000235:genetics; D002645:Chickens; D006801:Humans; D018625:Microscopy, Atomic Force; D020125:Mutation, Missense; D011817:Rabbits; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D000199:Actins; D030161:Avian Proteins; D029701:Saccharomyces cerevisiae Proteins