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Processivity of the single-headed kinesin KIF1A through biased binding to tubulin


Conventional isoforms of the motor protein kinesin behave functionally not as ‘single molecules’ but as ‘two molecules’ paired. This dimeric structure poses a barrier to solving its mechanism1,2,3,4. To overcome this problem, we used an unconventional kinesin KIF1A (refs 5, 6) as a model molecule. KIF1A moves processively as an independent monomer7,8, and can also work synergistically as a functional dimer9. Here we show, by measuring its movement with an optical trapping system10, that a single ATP hydrolysis triggers a single stepping movement of a single KIF1A monomer. The step size is distributed stochastically around multiples of 8 nm with a gaussian-like envelope and a standard deviation of 15 nm. On average, the step is directional to the microtubule's plus-end against a load force of up to 0.15 pN. As the source for this directional movement, we show that KIF1A moves to the microtubule's plus-end by 3 nm on average on binding to the microtubule, presumably by preferential binding to tubulin on the plus-end side. We propose a simple physical formulation to explain the movement of KIF1A.

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Figure 1: Movement of KIF1A beads.
Figure 2: Stepping movement of KIF1A beads.
Figure 3: Plus-end-directed movement after binding to the microtubule.


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We thank T. J. Mitchison for the gift of GMPCPP; H. Fukuda, H. Sato and M. Sugaya for technical and secretarial assistance; and J. Howard, M. Kikkawa and our colleagues for discussion. This work was supported by a Center of Excellence Grant-in-Aid (N.H.) and a Grant-in-Aid (H.H.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Correspondence to Nobutaka Hirokawa.

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Okada, Y., Higuchi, H. & Hirokawa, N. Processivity of the single-headed kinesin KIF1A through biased binding to tubulin. Nature 424, 574–577 (2003).

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