Directionality of dynein is controlled by the angle and length of its stalk

Can, Sinan; Lacey, Samuel E; Gür, Mert; Carter, Andrew P.; Yıldız, Ahmet

doi:10.1038/s41586-019-0914-z

Cited by 61 publications

(69 citation statements)

References 35 publications

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“…The present model can be extended to study the effects of the vectorial character of the applied load on the mechanics of dynein and myosin motors, since the load-velocity and -detachment rate behaviours of kinesins, dyneins, and myosins are similar [14][15][16][17]. This can help to understand the mechanics of collective function of different molecular motors, owing to the force-dependent interactions of the motors.…”

Section: (C) and 3(b)mentioning

confidence: 94%

“…They measured the vertical load component F z , where the horizontal component F x was resisting (<0, applied against the stepping direction). More recently, single-molecule optical trapping experiments [14][15][16][17] have studied the function of molecular motors under assisting loads F x (>0, applied in the stepping direction) as well. They have shown that the motors exhibit similar responses to the applied load direction: i) their velocity decreases with resisting loads, but changes slightly when the load is assisting, and ii) motors favor faster detachment rate under assisting loads than resisting ones.…”

Section: Introductionmentioning

confidence: 99%

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Processivity of molecular motors under vectorial loads

Khataee

Neufeld

2020

Preprint

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Molecular motors are cellular machines that drive the spatial organization of the cells by transporting cargoes along intracellular filaments. Although the mechanical properties of single molecular motors are relatively well characterised, it remains elusive how the three-dimensional geometry of a load imposed on a motor affects its processivity, i.e., the average distance that a motor moves per interaction with a filament. Here, we theoretically explore this question for a single kinesin molecular motor by analysing the load-dependence of the stepping and detachment processes. We find that the processivity of kinesin increases with lowering the load angle between kinesin and microtubule, due to the deceleration of the detachment rate. When the load angle is large, it is predicted that processivity can be enhanced if the velocity becomes less sensitive to load, through an optimal distribution of the load over the kinetic transition rates underlying a mechanical step of the motor. These results provide new insights into understanding of the design of potential synthetic biomolecular machines that can travel long distances with high velocities.

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Section: (C) and 3(b)mentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Processivity of molecular motors under vectorial loads

Khataee

Neufeld

2020

Preprint

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“…In broad brushstrokes, cytoplasmic dynein motors can be divided into two sub-families: mammalian and yeast dynein, or weak and strong dynein (according to their characteristic stalling force (3,4)), respectively. There is a burgeoning interest in these motors (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), in particular, their mechanism of motion and regulation. However, dynein's stepping mechanism remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

“…However, dynein's stepping mechanism remains largely unknown. Furthermore, in recent years, evidence emerged that, unlike kinesin, yeast cytoplasmic dynein motors (henceforth referred to as "dynein") are not limited to steps that are parallel to the MT long axis (x-axis), and in fact, they perform steps in all directions, such as in the direction of the MT short axis (y-axis) (5)(6)(7). While our primary focus in this work is yeast dynein, some conclusions will be drawn regarding mammalian cytoplasmic dynein.…”

Section: Introductionmentioning

confidence: 99%

Directional stepping model for yeast dynein: Longitudinal- and side- step distributions

Fayer

Granek

2019

Preprint

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We deduce the directional step distribution of yeast dynein motor protein on the microtubule surface by combing intrinsic features of the dynein and microtubule. These include the probability distribution of the separation vector between the two microtubule binding domains (MTBDs), the angular probability distribution of a single MTBD translation, the existence of a microtubule seam defect, microtubule binding sites, and theoretical extension that accounts for a load force on the motor. Our predictions are in excellent accord with the measured longitudinal step size distributions at various load forces. Moreover, we predict the side-step distribution and its dependence on longitudinal load forces, which shows a few surprising features. First, the distribution is broad. Second, in the absence of load, we find a small right-hand bias. Third, the side-step bias is susceptible to the longitudinal load force; it vanishes at a load equal to the motor stalling force and changes to a left-hand bias above that value. Fourth, our results are sensitive to the ability of the motor to explore the seam several times during its walk. While available measurements of side-way distribution are limited, our findings are amenable to experimental check and, moreover, suggest a diversity of results depending on whether the microtubule seam is viable to motor sampling. Significance StatementThe function of microtubule (MT) associated protein motors, kinesin and dynein, is essential for a myriad of intracellular processes. Different measurements on yeast cytoplasmic-dynein stepping characteristics appear to be unrelated to each other. We provide a unified physical-statistical model that combines these seemingly independent features with a theoretical expression that accounts for the exertion of a longitudinal load force, to yield the longitudinal step distribution at various load forces. The latter is in excellent accord with the measured distributions. Moreover, we deduce the side-step distribution, which surprisingly is susceptible to longitudinal load forces and comprises a right or left bias. This side-way bias is consistent with observations of helical motion of a nanoparticle carried by a number of motors.

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“…EM studies indicate that the dynein stalk in the MT-bound state tilts backward, with an angle of ~42º 32 . A recent study showed that the reverse kink mutant, which moves in the opposite direction, still possesses resistance to the minus-end force (i.e., as with the regular dynein motor) 33 , further supporting the binding mode of low-affinity MTBD and confirming that its interface geometry with respect to MTs is crucial for generating the directional preference of dynein motility.…”

Section: A Model Of Biased Movement Of Dyneinmentioning

confidence: 74%

Structural basis for two-way communication between dynein and microtubules

Nishida

Komori

Takarada

et al. 2019

Preprint

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The movements of cytoplasmic dynein on microtubule (MT) tracks is achieved by two-way communication between the microtubule-binding domain (MTBD) and the ATPase domain of dynein via an a-helical coiled-coil stalk, but the structural basis of this communication remains elusive. Here, we regulated MTBD either in high-affinity or low-affinity states by introducing a disulfide bond between the coiled-coils and analyzed the resulting structures by NMRand cryo-EM.In the MT-unbound state, the affinity changes of MTBD were achieved by sliding of the N-terminal α-helix by one half-turn, which suggests that structural changes propagate from the ATPase-domain to MTBD. In addition, cryo-EM analysis showed that MT binding induced further sliding of the N-terminal α-helix even without the disulfide bond, which suggests the MT-induced conformational changes propagate toward the ATPase domain. Based on differences in the MT-binding surface between the high-and low-affinity states, we propose a potential mechanism for the directional bias of dynein movement on MT tracks. Nishida et al.

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Directionality of dynein is controlled by the angle and length of its stalk

Cited by 61 publications

References 35 publications

Processivity of molecular motors under vectorial loads

Processivity of molecular motors under vectorial loads

Directional stepping model for yeast dynein: Longitudinal- and side- step distributions

Structural basis for two-way communication between dynein and microtubules

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