biostudies-literature00440Wulf SFNIDCD NIH HHSNIGMS NIH HHSE1844-52https://www.ebi.ac.uk/biostudies/studies/S-EPMC4822626biostudies-literatureUnknown113(13)Molecular motors produce force when they interact with their cellular tracks. For myosin motors, the primary force-generating state has MgADP tightly bound, whereas myosin is strongly bound to actin. We have generated an 8-Å cryoEM reconstruction of this state for myosin V and used molecular dynamics flexed fitting for model building. We compare this state to the subsequent state on actin (Rigor). The ADP-bound structure reveals that the actin-binding cleft is closed, even though MgADP is tightly bound. This state is accomplished by a previously unseen conformation of the β-sheet underlying the nucleotide pocket. The transition from the force-generating ADP state to Rigor requires a 9.5° rotation of the myosin lever arm, coupled to a β-sheet rearrangement. Thus, the structure reveals the detailed rearrangements underlying myosin force generation as well as the basis of strain-dependent ADP release that is essential for processive myosins, such as myosin V.Proceedings of the National Academy of Sciences of the United States of AmericaForce-producing ADP state of myosin bound to actin.PMC4822626P41 GM103311R01 DC009100P41-GM103311DC009100Fujita-Becker SOster MSweeney HLPylypenko OHoudusse AMRopars VTrabuco LGWulf SFHofhaus GSchroder RR44falseForce-producing ADP state of myosin bound to actin.Molecular motors produce force when they interact with their cellular tracks. For myosin motors, the primary force-generating state has MgADP tightly bound, whereas myosin is strongly bound to actin. We have generated an 8-Å cryoEM reconstruction of this state for myosin V and used molecular dynamics flexed fitting for model building. We compare this state to the subsequent state on actin (Rigor). The ADP-bound structure reveals that the actin-binding cleft is closed, even though MgADP is tightly bound. This state is accomplished by a previously unseen conformation of the β-sheet underlying the nucleotide pocket. The transition from the force-generating ADP state to Rigor requires a 9.5° rotation of the myosin lever arm, coupled to a β-sheet rearrangement. Thus, the structure reveals the detailed rearrangements underlying myosin force generation as well as the basis of strain-dependent ADP release that is essential for processive myosins, such as myosin V.2016-01-01T00:00:00Z2016 Mar2024-11-21T08:50:50.005Z2019-03-27T03:11:21ZS-EPMC48226262697659410.1073/pnas.1516598113