Figure 1. | Examining kinesin processivity within a general gating framework

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Examining kinesin processivity within a general gating framework

Figure 1.

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Stanford University, United States; Pennsylvania State University, United States
Figure 1.
Download figureOpen in new tabFigure 1. A general gating framework based on mechanical states of dimeric motors.

(A) The kinesin mechanochemical cycle. Kinesin starts from the one-head-bound (1-HB) ATP-waiting state [α], characterized by a strongly bound, nucleotide-free (Ø) front head (red) and an unbound, ADP-containing tethered head (blue). ATP binding induces a force-dependent transition involving partial NL docking, shifting the tethered head past the bound head [β1]. ATP hydrolysis completes NL docking and facilitates tethered-head binding [β2]. At this point, kinesin may access a dissociated state [Off], induced by premature phosphate release from the bound head, leading to dimer detachment. However, if the tethered head reaches the forward MT binding site and completes the step before the bound head can dissociate, kinesin enters the two-heads-bound (2-HB) state [γ]. Rear-head release returns the dimer to the ATP-waiting state [α], having moved forward by 8.2 nm. (B) A simplified general gating framework, based on the cycle in (A). Stepping, binding, and unbinding gates are shown with associated rate constants between each of the three gated states, [A], [B], and [C]. The cycle begins at the 1-HB ATP-waiting state [A], where the stepping gate promotes processivity by inhibiting rear-head (blue) rebinding and premature bound-head (red) release. Following a force-dependent step that shifts the tethered head past the bound head [B], the binding gate promotes binding of the tethered head at the forward MT binding site while inhibiting release of the bound head. Also shown is a competing dissociated state [Off], arising from premature release of the bound head from the 1-HB state, accessible from either [A] or [B]. Tethered-head binding leads to the 2-HB state [C], where the unbinding gate promotes rear-head release while inhibiting front-head release, returning the motor to the start of the cycle [A].