Actin depolymerization under force is governed by lysine 113:glutamic acid 195-mediated catch-slip bonds

Area of Science:

• Biophysics
• Cell Biology
• Structural Biology

Background:

• Actin filaments are crucial cytoskeletal components that undergo constant force-induced dynamics.
• The precise mechanisms by which external forces regulate actin dynamics remain largely unknown.

Purpose of the Study:

• To investigate how tensile force influences the dissociation kinetics of actin subunits.
• To elucidate the molecular basis of force-dependent regulation of actin dynamics.

Main Methods:

• Atomic force microscopy (AFM) force-clamp experiments were employed to measure dissociation kinetics.
• Steered molecular dynamics (MD) simulations were utilized to explore force-induced structural changes.
• Site-directed mutagenesis was performed on yeast actin to validate structural findings.

Main Results:

• Tensile force alters G-actin/G-actin and G-actin/F-actin dissociation, exhibiting catch bonds at low forces and slip bonds above a threshold.
• MD simulations revealed force-induced salt bridges, such as Lysine 113 (K113):Glutamic acid 195 (E195), contributing to catch-slip bond behavior.
• Mutations K113S and E195S in yeast actin abolished the observed catch bond phenomenon.

Conclusions:

• Actin filaments exhibit force-dependent catch-slip bond behavior, a novel mechanoregulatory mechanism.
• A structural basis for actin catch-slip bonds involving specific inter-subunit interactions has been identified.
• This mechanism may regulate cellular functions by controlling the depolymerization of force-bearing actin filaments.