Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and P<sub>i</sub> Release
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 P<sub>i</sub> relea...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/1/104 |
| _version_ | 1797543622245089280 |
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| author | Peter Franz Wiebke Ewert Matthias Preller Georgios Tsiavaliaris |
| author_facet | Peter Franz Wiebke Ewert Matthias Preller Georgios Tsiavaliaris |
| author_sort | Peter Franz |
| collection | DOAJ |
| description | 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 P<sub>i</sub> 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 P<sub>i</sub> 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. |
| first_indexed | 2024-03-10T13:48:14Z |
| format | Article |
| id | doaj.art-3498e45845464feab5592280a6882c3c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:48:14Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3498e45845464feab5592280a6882c3c2023-11-21T02:26:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-0122110410.3390/ijms22010104Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and P<sub>i</sub> ReleasePeter Franz0Wiebke Ewert1Matthias Preller2Georgios Tsiavaliaris3Cellular Biophysics, Institute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, GermanyStructural Bioinformatics and Chemical Biology, Institute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, GermanyStructural Bioinformatics and Chemical Biology, Institute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, GermanyCellular Biophysics, Institute for Biophysical Chemistry, Hannover Medical School, 30625 Hannover, GermanyThe 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 P<sub>i</sub> 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 P<sub>i</sub> 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.https://www.mdpi.com/1422-0067/22/1/104myosinactinATPase cycletransient kineticsduty ratioallosteric communication |
| spellingShingle | Peter Franz Wiebke Ewert Matthias Preller Georgios Tsiavaliaris Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and P<sub>i</sub> Release International Journal of Molecular Sciences myosin actin ATPase cycle transient kinetics duty ratio allosteric communication |
| title | Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and P<sub>i</sub> Release |
| title_full | Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and P<sub>i</sub> Release |
| title_fullStr | Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and P<sub>i</sub> Release |
| title_full_unstemmed | Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and P<sub>i</sub> Release |
| title_short | Unraveling a Force-Generating Allosteric Pathway of Actomyosin Communication Associated with ADP and P<sub>i</sub> Release |
| title_sort | unraveling a force generating allosteric pathway of actomyosin communication associated with adp and p sub i sub release |
| topic | myosin actin ATPase cycle transient kinetics duty ratio allosteric communication |
| url | https://www.mdpi.com/1422-0067/22/1/104 |
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