TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Franz, Peter
A1  - Ewert, Wiebke
A1  - Preller, Matthias
A1  - Tsiavaliaris, Georgios
T1  - Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and Pi Release
JF  - International Journal of Molecular Sciences
N2  - The actomyosin system generates mechanical work with the execution of the power stroke, an ATP-driven, two-step rotational swing of the myosin-neck that occurs post ATP hydrolysis during the transition from weakly to strongly actin-bound myosin states concomitant with Pi release and prior to ADP dissociation. The activating role of actin on product release and force generation is well documented; however, the communication paths associated with weak-to-strong transitions are poorly characterized. With the aid of mutant analyses based on kinetic investigations and simulations, we identified the W-helix as an important hub coupling the structural changes of switch elements during ATP hydrolysis to temporally controlled interactions with actin that are passed to the central transducer and converter. Disturbing the W-helix/transducer pathway increased actin-activated ATP turnover and reduced motor performance as a consequence of prolonged duration of the strongly actin-attached states. Actin-triggered Pi release was accelerated, while ADP release considerably decelerated, both limiting maximum ATPase, thus transforming myosin-2 into a high-duty-ratio motor. This kinetic signature of the mutant allowed us to define the fractional occupancies of intermediate states during the ATPase cycle providing evidence that myosin populates a cleft-closure state of strong actin interaction during the weak-to-strong transition with bound hydrolysis products before accomplishing the power stroke.
KW  - allosteric communication
KW  - duty ratio
KW  - actin
KW  - transient kinetics
KW  - ATPase cycle
KW  - myosin
KW  - force generation
KW  - power stroke
Y1  - 2021
UN  - https://nbn-resolving.org/urn:nbn:de:hbz:1044-opus-52802
SN  - 1422-0067
SS  - 1422-0067
U6  - https://doi.org/10.3390/ijms22010104
DO  - https://doi.org/10.3390/ijms22010104
PM  - 33374308
VL  - 22
IS  - 1
SP  - 19
S1  - 19
PB  - MDPI
CY  - Basel
ER  -