Kinesin Moves by an Asymmetric Hand-Over-Hand Mechanism

Asbury, Charles L.; Fehr, Adrian N.; Block, Steven M.

doi:10.1126/science.1092985

Cited by 483 publications

(476 citation statements)

References 28 publications

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“…Single molecule experiments using optical tweezers [134][135][136] and fluorescence dye 137,138 suggested that kinesin undergoes structural transitions resulting in an alternative binding of motor head to the microtubule binding sites that are 8-nm apart. The force-ATP-velocity (or force-ATP-randomness) relationship measured through the single molecule assays and kinetic ensemble experiments prompted several groups to decipher the energy landscape of motor dynamics by proposing and solving the phenomenological models that best describe the motility data.…”

Section: Kinesinmentioning

confidence: 99%

Minimal Models for Proteins and RNA: From Folding to Function

Pincus

Cho

Hyeon

et al. 2008

Progress in Molecular Biology and Translational Science

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We present a panoramic view of the utility of coarse-grained (CG) models to study folding and functions of proteins and RNA. Drawing largely on the methods developed in our group over the last twenty years, we describe a number of key applications ranging from folding of proteins with disulfide bonds to functions of molecular machines. After presenting the theoretical basis that justifies the use of CG models, we explore the biophysical basis for the emergence of a finite number of folds from lattice models. The lattice model simulations of approach to the folded state show that non-native interactions are relevant only early in the folding process -a finding that rationalizes the success of structure-based models that emphasize native interactions. Applications of off-lattice C α and models that explicitly consider side chains (C α -SCM) to folding of β-hairpin and effects of macromolecular crowding are briefly discussed. Successful applications of a new class of off-lattice models, referred to as the Self- We also present two distinct models for RNA, namely, the Three Site Interaction (TIS) model and the SOP model, that probe forced unfolding and force quench refolding of a simple hairpin and Azoarcus ribozyme. The unfolding pathways of Azoarcus ribozyme depend on the loading rate, while constant force and constant loading rate simulations of the hairpin show that both forced-unfolding and force-quench refolding pathways are heterogeneous. The location of the transition state moves as force is varied. The predictions based on the SOP model show that force-induced unfolding pathways of the ribozyme can be dramatically changed by varying the loading rate. We conclude with a discussion of future prospects for the use of coarse-grained models in addressing problems of outstanding interest in biology.

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Section: Kinesinmentioning

confidence: 99%

Minimal Models for Proteins and RNA: From Folding to Function

Pincus

Cho

Hyeon

et al. 2008

Progress in Molecular Biology and Translational Science

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“…Experiments with mutants that uncouple phosphate (P i ) release and motor detachment from the microtubule were used to determine the order of steps K5-K7, in which P i release is rate-limiting [24]. With each cycle, the two motor heads exchange position, progressing in an asymmetric hand-over-hand fashion [25][26][27].…”

Section: A Consensus Mechanochemical Cycle For Dimeric Kinesinmentioning

confidence: 99%

To step or not to step? How biochemistry and mechanics influence processivity in Kinesin and Eg5

Valentine

Gilbert

2007

Current Opinion in Cell Biology

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Conventional kinesin and Eg5 are essential nanoscale motor proteins. Single-molecule and presteady-state kinetic experiments indicate that both motors use similar strategies to generate movement along microtubules, despite having distinctly different in vivo functions. Single molecules of kinesin, a long-distance cargo transporter, are highly processive, binding the microtubule and taking 100 or more sequential steps at velocities of up to 700 nm/s before dissociating, whereas Eg5, a motor active in mitotic spindle assembly, is also processive, but takes fewer steps at a slower rate. By dissecting the structural, biochemical and mechanical features of these proteins, we hope to learn how kinesin and Eg5 are optimized for their specific biological tasks, while gaining insight into how biochemical energy is converted into mechanical work.

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“…For example, the dimeric kinesin-1 transports cargo by taking 8 nm steps in a hand-over-hand fashion along microtubules (2)(3)(4)(5). Microtubules consist of circularly arranged protein chains, socalled protofilaments, assembled of a/b-tubulin dimers (1).…”

Section: Introductionmentioning

confidence: 99%

The Kinesin-8 Kip3 Switches Protofilaments in a Sideward Random Walk Asymmetrically Biased by Force

Bugiel

Böhl

Schäffer

2015

Biophysical Journal

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Molecular motors translocate along cytoskeletal filaments, as in the case of kinesin motors on microtubules. Although conventional kinesin-1 tracks a single microtubule protofilament, other kinesins, akin to dyneins, switch protofilaments. However, the molecular trajectory-whether protofilament switching occurs in a directed or stochastic manner-is unclear. Here, we used high-resolution optical tweezers to track the path of single budding yeast kinesin-8, Kip3, motor proteins. Under applied sideward loads, we found that individual motors stepped sideward in both directions, with and against loads, with a broad distribution in measured step sizes. Interestingly, the force response depended on the direction. Based on a statistical analysis and simulations accounting for the geometry, we propose a diffusive sideward stepping motion of Kip3 on the microtubule lattice, asymmetrically biased by force. This finding is consistent with previous multimotor gliding assays and sheds light on the molecular switching mechanism. For kinesin-8, the diffusive switching mechanism may enable the motor to bypass obstacles and reach the microtubule end for length regulation. For other motors, such a mechanism may have implications for torque generation around the filament axis.

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Kinesin Moves by an Asymmetric Hand-Over-Hand Mechanism

Cited by 483 publications

References 28 publications

Minimal Models for Proteins and RNA: From Folding to Function

Minimal Models for Proteins and RNA: From Folding to Function

To step or not to step? How biochemistry and mechanics influence processivity in Kinesin and Eg5

The Kinesin-8 Kip3 Switches Protofilaments in a Sideward Random Walk Asymmetrically Biased by Force

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