The structure of the rigor complex and its implications for the power stroke

Abstract

Decorated actin provides a model system for studying the strong interaction between actin and myosin. Cryo-energy-filter electron microscopy has recently yielded a 14 Å resolution map of rabbit skeletal actin decorated with chicken skeletal S1. The crystal structure of the cross-bridge from skeletal chicken myosin could not be fitted into the three-dimensional electron microscope map without some deformation. However, a newly published structure of the nucleotide-free myosin V cross-bridge, which is apparently already in the strong binding form, can be fitted into the three-dimensional reconstruction without distortion. This supports the notion that nucleotide-free myosin V is an excellent model for strongly bound myosin and allows us to describe the actin-myosin interface. In myosin V the switch 2 element is closed although the lever arm is down (post-power stroke). Therefore, it appears likely that switch 2 does not open very much during the power stroke. The myosin V structure also differs from the chicken skeletal myosin structure in the nucleotide-binding site and the degree of bending of the backbone b-sheet. These suggest a mechanism for the control of the power stroke by strong actin binding.

Molecular mechanism of actomyosin-based motility

“…However, only the deletion of D590 affected the basal ATPase, which was elevated almost 10-fold. Structural studies have shown that D590 (D570 in chicken myosin-V) experiences the largest conformational changes upon cleft closure, when the region undergoes a helix-to-loop transition [24,65,117,118].…”

The motor mechanism of myosin V: insights for muscle contraction

“…It corresponds to the ATP-state of the motor that detaches from actin at the end of the cross-bridge cycle. Only the recently published myosin V nucleotide-free structure has a closed cleft (Coureux et al 2003) necessary for strong actin binding, and thus it fits even the myosin II cryoEM maps better than the myosin II post-rigour structures (Holmes et al 2004).…”

“…(Compare the docking of post-rigour in figure 2 with the docking of rigour in figure 8. More detail is given in the contribution to this issue by Holmes et al (2004).) This movement is necessary to generate a strong binding interface with actin, as myosin in the post-rigour conformation binds weakly to actin.…”

Dynamics of actomyosin interactions in relation to the cross-bridge cycle

“…the weak to strong transition states associated with the AÁMccÁDÁP to AÁMocÁDÁP transition (Bershitsky et al 1997). More recently, Holmes et al (2004) have suggested a structural model in which the strong binding of actin allows the lever arm to swing without the opening of switch 2. While this model provides another mechanism for avoiding futile cycling, our data with ATPcS lend no support for this idea, as will be discussed elsewhere (Conibear et al 2004).…”