Fig. 1. Tentative schemes for conformational changes during ATPase cycles. (A) Motor acting as a monomer to contribute, in this case, to minus-end-directed movement. The motor domain is shown in cyan with the switch II helix in orange, the coiled-coil neck in red. The second head, thought to move passively with the coiled-coil, is not shown. The nucleotide bound to the motor is indicated at each stage in the cycle. (1) ADP-bound motor domain waiting to make contact with tubulin (part of one protofilament in a microtubule is shown as green subunits). The coiled-coil neck (red) is docked on to the motor domain. (2) Contact is made, ADP is released and the empty motor domain binds strongly to tubulin. (3) ATP binds to the nucleotide pocket. The coiled-coil, no longer docked on to the ATP-filled motor domain, is free to swing towards the MT minus end and allow other motors on the same cargo to search for new sites while this one remains attached. In an alternative model (Yun et al., 2003), the coiled-coil would be released by the loss of ADP and be free to move at stage 2. (4) ATP is hydrolysed to ADP and phosphate (Pi). (5) The motor domain detaches as phosphate is lost. Whilst the motor is unattached, the neck docks back on to the ADP-bound motor domain. (B) Processive dimer, whose two heads take turns in stepping towards the plus end of the MT (Vale et al., 1996; Schnitzer and Block, 1997; Hancock and Howard, 1998; Young et al., 1998; Carter and Cross, 2005; Hackney, 2007). White letters (E, D, T, DP) indicate the nucleotide states of individual heads. (1) The tethered, ADP-bound lead head is free to find a new binding site. It needs to swing around the junction with the neck-linker (red line) to bind to the same protofilament as the rear head. (2) ADP is released on contact and the empty lead head binds strongly. It must wait for the trailing head to finish ATP hydrolysis, release phosphate and detach (Klumpp et al., 2004), then wait to bind fresh ATP itself. The presence of the tethered head on the top of the leading head may provide the signal that allows ATP to bind. (3) ATP binds and the neck-linker is able to dock on to a site (shown as a white line) on the motor domain that helps to bias the binding of the new lead head to a site in the plus direction. (4) ATP is hydrolysed, making detachment possible once the lead head is firmly bound. (5) The detached head parks on top of the lead head while this head waits for ATP to bind (see main text and Fig. 6). In moving from position 4 to 5 and back to 1, the tethered heads must pass the coiled-coil on different sides during alternate steps, to avoid building up a twist.