Kinesin’s Front Head Is Gated by the Backward Orientation of Its Neck Linker

Dogan, Merve Yusra; Can, Sinan; Cleary, Frank B.; Purde, Vedud; Yıldız, Ahmet

doi:10.1016/j.celrep.2015.02.061

Cited by 55 publications

(47 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, during a forward step, the P i release in the trailing head can occur simultaneously with the ADP release, ATP binding, and then ATP hydrolysis in the leading head. Thus, we consider that the tension on the NL has no effect on the rate constant of P i release; that is, the rate constant of P i release is independent of the external load acting on the bead attached to the coiled-coil stalk of the dimer, which is also consistent with the recent single-molecule data [57]. However, we consider that the rate constant of P i release is dependent on the pointing direction of its NL.…”

Section: Value Dmksupporting

confidence: 90%

Processivity of dimeric kinesin‐1 molecular motors

et al. 2018

View full text Add to dashboard Cite

Kinesin‐1 is a homodimeric motor protein that can move along microtubule filaments by hydrolyzing ATP with a high processivity. How the two motor domains are coordinated to achieve such high processivity is not clear. To address this issue, we computationally studied the run length of the dimer with our proposed model. The computational data quantitatively reproduced the puzzling experimental data, including the dramatically asymmetric character of the run length with respect to the direction of external load acting on the coiled‐coil stalk, the enhancement of the run length by addition of phosphate, and the contrary features of the run length for different types of kinesin‐1 with extensions of their neck linkers compared with those without extension of the neck linker. The computational data on other aspects of the movement dynamics such as velocity and durations of one‐head‐bound and two‐head‐bound states in a mechanochemical coupling cycle were also in quantitative agreement with the available experimental data. Moreover, predicted results are provided on dependence of the run length upon external load acting on one head of the dimer, which can be easily tested in the future using single‐molecule optical trapping assays.

show abstract

Section: Value Dmksupporting

confidence: 90%

Processivity of dimeric kinesin‐1 molecular motors

et al. 2018

View full text Add to dashboard Cite

show abstract

“…However, a greater number of metastable states, each representing a persistent conformation or ligand binding status of a biomolecular machine, make possible a larger array of schemes for the following: interaction, such as distinct binding affinities [32]; machine operation, such as 'gating' [33]; and regulation through variable action on distinct states [34].…”

Section: Resultsmentioning

confidence: 99%

Allocating dissipation across a molecular machine cycle to maximize flux

Brown

Sivak

2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Biomolecular machines consume free energy to break symmetry and make directed progress. Nonequilibrium ATP concentrations are the typical free energy source, with one cycle of a molecular machine consuming a certain number of ATP, providing a fixed free energy budget. Since evolution is expected to favor rapid-turnover machines that operate efficiently, we investigate how this free energy budget can be allocated to maximize flux. Unconstrained optimization eliminates intermediate metastable states, indicating that flux is enhanced in molecular machines with fewer states. When maintaining a set number of states, we show that-in contrast to previous findings-the fluxmaximizing allocation of dissipation is not even. This result is consistent with the coexistence of both 'irreversible' and reversible transitions in molecular machine models that successfully describe experimental data, which suggests that in evolved machines different transitions differ significantly in their dissipation.

show abstract

“…Andreasson show using neck linker truncations that mechanical strain is not the key to coordinated stepping; rather, it is neck linker docking and undocking that matters. Dogan et al apply force‐ramps to single tethered kinesin heads and demonstrate a strong dependence of the detachment force on the direction of the load, with backwards load (and neck linker undocking) stabilizing microtubule binding, and forwards load (and neck linker docking) destabilizing.…”

Section: Neck Linker Docking Force Generation and Force‐sensingmentioning

confidence: 99%

Review: Mechanochemistry of the kinesin‐1 ATPase

Cross

2016

Biopolymers

View full text Add to dashboard Cite

Kinesins are P‐loop NTPases that can do mechanical work. Like small G‐proteins, to which they are related, kinesins execute a program of active site conformational changes that cleaves the terminal phosphate from an NTP substrate. But unlike small G‐proteins, kinesins can amplify and harness these conformational changes in order to exert force. In this short review I summarize current ideas about how the kinesin active site works and outline how the active site chemistry is coupled to the larger‐scale structural cycle of the kinesin motor domain. Focusing largely on kinesin‐1, the best‐studied kinesin, I discuss how the active site switch machinery of kinesin cycles between three distinct states, how docking of the neck linker stabilizes two of these states, and how tension‐sensitive and position‐sensitive neck linker docking may modulate both the hydrolysis step of ATP turnover and the trapping of product ADP in the active site. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 476–482, 2016.

show abstract

Kinesin’s Front Head Is Gated by the Backward Orientation of Its Neck Linker

Cited by 55 publications

References 38 publications

Processivity of dimeric kinesin‐1 molecular motors

Processivity of dimeric kinesin‐1 molecular motors

Allocating dissipation across a molecular machine cycle to maximize flux

Review: Mechanochemistry of the kinesin‐1 ATPase

Contact Info

Product

Resources

About