Moreover, the trailing head of M5-HMM would not be able to bind to actin when AMPPNP (mimicking the posthydrolysis ADP Pi) is bound to the trailing head because the head is supposed to assume a prestroke conformation (i.e., bent neck motor domain junction).
(K ) For a motor to step, the trailing head of motor (motor 2) pivots about the lead head and its binding site is determined by the following criteria: (a) The binding site must be 36 ± 7.2 nm pixel from the leading head (gray arc).
Even in the presence of ADP, the foot stomp occurs at both leading and trailing heads of a two-headed bound molecule, with more frequent occurrence at the leading head than at the trailing head.
Other structural schemes have been proposed in order to account for differences in nucleotide-binding and other properties between the leading and trailing heads of kinesin (Hirokawa et al., 2009; Sindelar, 2011).
Importantly, binding of ATP in the leading head at this point in the cycle promotes a forward step by the trailing head through docking of the neck linker but does not prevent a backward step because neck linker docking is only weakly supported in the motor's ATP state (Rice et al., 2003).
One is the 'mechanical gate model' in which the power stroke of the leading head accelerates the detachment of the trailing head (Hancock and Howard, 1999), meaning the gating contributes to the velocity of the molecules (see Supplementary Discussion for details).
Conversely, acceleration of trailing head detachment by mechanical strain transmitted from the leading head may represent an unusual stimulatory gating process, but there are disagreements concerning the magnitude and mechanistic significance of this process (4, 23, 24).
From the two head bound state of myosin 5a, the trailing head detaches from actin upon binding of ATP.
The other is the 'chemical gate model' according to which ATP binding of the leading head is inhibited until detachment of the trailing head occurs, meaning only the trailing head can become weak binding and subsequently detach from the MT (Rosenfeld et al, 2003; Klumpp et al, 2004).
The foot stomp of the leading head was observed about 3 times more often than stomping of the trailing head.
Therefore, ATP binding itself should supply the energy for breaking the rigor bond of the trailing head.
