WHERE IN THE KINESIN BIOCHEMICAL PATHWAY IS FORWARD MOTION PRODUCED?
According to Hancock and Howard (27), release of stored strain upon unbinding of the trailing head permits the leading head to power an 8-nm advance of the entire molecule. According to Rice et al. (32), ATP binding induces the docking of the neck linker on the leading head to produce motion of the partner head. My own group has found that the effective binding rate for ATP is load-dependent, which indicates that ATP binding, or a transition closely coupled to it, generates the forward step (33). When taken together with other biochemical results, modeling of our data suggests that ATP binding is highly reversible and followed by some kind of conformational (and less reversible) change, leading to a mechanical step broadly consistent with the model of Rice et al. (32). The recent finding by Guydosh and Block (8) that the duration of the terminal backstep before the resumption of forward movement (from a pause induced by a nucleotide analog) depends on ATP concentration strengthens the
