Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules

Imai, Haruo; Shima, Tomohiro; Sutoh, Kazuo; Walker, Matthew; Knight, Peter J.; Kon, Takahide; Burgess, Simon

doi:10.1038/ncomms9179

Cited by 69 publications

(109 citation statements)

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“…Change point analysis (44) was used to detect abrupt changes in α or β (or both) objectively with 95% confidence. Contrary to expectations based on EM imaging in the plane of the dynein ring (30)(31)(32)35), rotational changes in α and β were similar in both frequency and magnitude ( Fig. 3 B and C), with <jΔαj> = 6.7°± 0.17°(SEM) and <jΔβj> = 5.47°± 0.1°(SEM).…”

Section: Resultscontrasting

confidence: 44%

“…This flexibility can account for the variability of dynein stepping patterns. Together with recent EM data (30,35), our observations support a unique stepping mechanism for an essential cellular motor based on docking of the linker and flexing of the stalk.…”

mentioning

confidence: 65%

“…Rotational motions of the ring thus depend on these forces and the mechanical compliance of the stalk and MTBD hinge. Previous EM studies of axonemal dynein suggest that there is a slight bending of the stalk during translocation (35), whereas EM studies of isolated cytoplasmic dyneins support the presence of a hinge at the MTBD (30). Because both bending of the stalk and hinging at the MTBD could explain our observed small ring rotations, we performed an MD simulation for a system comprising the dynein stalk and MTBD to examine the contributions of stalk flexing and hinging to the overall flexibility.…”

Section: Resultsmentioning

confidence: 99%

“…This model is consistent with the elegant EM studies looking at dynein bound to MTs in both primed and unprimed conformations. These structural approaches suggest only small differences in orientation of the ring relative to the MT between the two states (30,35).…”

Section: Discussionmentioning

confidence: 99%

“…1A) (29). EM studies with both cytoplasmic (30,31) and axonemal (32) dynein provide some support for stalk rotation. Rotations of the ring may enable dynein to reach various tubulin subunits during a step (33).…”

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confidence: 99%

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Angular measurements of the dynein ring reveal a stepping mechanism dependent on a flexible stalk

Lippert

Dadosh

Hadden

et al. 2017

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

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The force-generating mechanism of dynein differs from the forcegenerating mechanisms of other cytoskeletal motors. To examine the structural dynamics of dynein's stepping mechanism in real time, we used polarized total internal reflection fluorescence microscopy with nanometer accuracy localization to track the orientation and position of single motors. By measuring the polarized emission of individual quantum nanorods coupled to the dynein ring, we determined the angular position of the ring and found that it rotates relative to the microtubule (MT) while walking. Surprisingly, the observed rotations were small, averaging only 8.3°, and were only weakly correlated with steps. Measurements at two independent labeling positions on opposite sides of the ring showed similar small rotations. Our results are inconsistent with a classic power-stroke mechanism, and instead support a flexible stalk model in which interhead strain rotates the rings through bending and hinging of the stalk. Mechanical compliances of the stalk and hinge determined based on a 3.3-μs molecular dynamics simulation account for the degree of ring rotation observed experimentally. Together, these observations demonstrate that the stepping mechanism of dynein is fundamentally different from the stepping mechanisms of other well-studied MT motors, because it is characterized by constant small-scale fluctuations of a large but flexible structure fully consistent with the variable stepping pattern observed as dynein moves along the MT.ynein is a molecular motor that walks processively toward the minus end of microtubules (MTs) in an ATP-dependent manner (1-3). Axonemal dyneins drive the motility of eukaryotic cilia and flagella, whereas cytoplasmic dynein is responsible for a wide range of functions within eukaryotic cells, including the retrograde transport of cargo such as autophagosomes in neurons (4), alignment of the mitotic spindle (5, 6), and chromosome segregation during mitosis (7). Disruption of dynein-mediated neuronal transport has been implicated in neurodegeneration (8), and mutations in dynein and dynein-associated proteins can cause a range of diseases, including spinal muscular atrophy (9, 10), lissencephaly (11) and Charcot-Marie-Tooth disease type 2 (reviewed in ref. 12). Despite the importance of dynein function, the mechanism by which dynein walks along the MT is not yet well understood.The motor domains of dynein are formed from six concatenated AAA domains, interrupted by a long, antiparallel, coiled-coil stalk that emerges from AAA4 and terminates in the microtubulebinding domain (MTBD) and the buttress that extends from AAA5 and is thought to stabilize the stalk (13,14). Two motor domains form a dimer via their N-terminal tails (2, 3). ATP binding and hydrolysis drive dynein mechanochemistry; the binding of ATP to AAA1 induces a conformational change leading to dissociation of the MTBD from the MT. Hydrolysis on the dissociated head induces a primed conformation that then rebinds to the MT. The forward step, or power stroke,...

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Section: Resultscontrasting

confidence: 44%

mentioning

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Angular measurements of the dynein ring reveal a stepping mechanism dependent on a flexible stalk

Lippert

Dadosh

Hadden

et al. 2017

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

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Atomic‐Level Coupled Interfaces and Lattice Distortion on CuS/NiS₂ Nanocrystals Boost Oxygen Catalysis for Flexible Zn‐Air Batteries

Luo

et al. 2017

Adv Funct Materials

225

133

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The exploration of highly efficient nonprecious metal bifunctional electrocatalysts to boost oxygen evolution reaction and oxygen reduction reaction is critical for development of high energy density metal-air batteries. Herein, a class of CuS/NiS 2 interface nanocrystals (INs) catalysts with atomic-level coupled nanointerface, subtle lattice distortion, and plentiful vacancy defects is reported. The results from temperature-dependent in situ synchrotron-based X-ray absorption fine spectroscopy and electron spin resonance spectroscopy demonstrate that the lattice distortion of 14.7% in CuS/NiS 2 caused by the strong Jahn-Teller effect of Cu, the strong atomic-level coupled interface of CuS and NiS 2 domains, and distinct vacancy defects can provide numerous effective active sites for their excellent bifunctional performance. A liquid Zn-air battery with the CuS/NiS 2 INs as air electrode displays a large peak power density (172.4 mW cm −2 ), a high specific capacity (775 mAh g Zn −1 ), and long cycle life (up to 83 h), making the CuS/NiS 2 INs among the best bifunctional catalysts for Zn-air battery. More remarkably, the flexible CuS/NiS 2 INsbased solid-state Zn-air batteries can power the LED after twisting, making them be promising in portable and wearable electronic devices.

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Colloidal Active Matter Mimics the Behavior of Biological Microorganisms—An Overview

Nsamela

Zintzun

Montenegro‐Johnson

et al. 2022

Small

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resources from the environment into building blocks and provides energy, and the capacity to pass on some form of inheritable information to the next generation. [1] The creation of artificial life-able to replicate these behaviors-is extensively studied with droplets, vesicles, [2] and DNA nanotechnology. [3] However, these exciting approaches belong to synthetic biology and are reviewed in detail in other excellent reviews. [4] While bio-inspiration has long been a driver for game-changing developments such as airplanes, submarines, radar, and water-repelling surfaces, on the small scale we see yet relatively few such developments. [5] There are fascinating micro-organisms that have evolved over billions of years, and over the course of this process they managed to adapt in different environments. The integration of living beings into their environment is a dynamic process that requires reaction and adaptation to external conditions and stimuli; it is all the more impressive, therefore, that some bacteria have adapted to water and land, but socalled thermo-and extremophiles have even adapted to survive the harshest conditions. Potential uses for smart small scale devices are plentiful, and range from drug delivery to sensing and environmental remediation, with specific literature available on all of these. [6][7][8] The first step is often assumed to be the ability to sense certain physical or chemical changes in the surroundings, and then evaluate which condition is more favorable and adapt accordingly. Artificial micromotors mimic biological microswimmers (Figure 1) in a fully synthetic way, giving microdevices motility, previously the attribute of living systems. Due to the small scale of these devices, their sensing and signal processing capabilities are very limited; yet still, several resemblances with living microswimmers have been observed and studied, and often impressive similarities or even additional understanding can be found. The goal of this review paper is to summarize recent progress in this area, and to give insight into the physical backgrounds of such biomimetic behaviors. Comparison of Biological and Synthetic Active MatterBiological microorganisms, often referred to as "microbes," are a highly diversified collection of living entities from all three branches of the tree of life: Bacteria and Archaea, which are This article provides a review of the recent development of biomimicking behaviors in active colloids. While the behavior of biological microswimmers is undoubtedly influenced by physics, it is frequently guided and manipulated by active sensing processes. Understanding the respective influences of the surrounding environment can help to engineering the desired response also in artificial swimmers. More often than not, the achievement of biomimicking behavior requires the understanding of both biological and artificial microswimmers swimming mechanisms and the parameters inducing mechanosensory responses. The comparison of both classes of microswimmers provides with analogies in thei...

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Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules

Cited by 69 publications

References 69 publications

Angular measurements of the dynein ring reveal a stepping mechanism dependent on a flexible stalk

Angular measurements of the dynein ring reveal a stepping mechanism dependent on a flexible stalk

Atomic‐Level Coupled Interfaces and Lattice Distortion on CuS/NiS₂ Nanocrystals Boost Oxygen Catalysis for Flexible Zn‐Air Batteries

Colloidal Active Matter Mimics the Behavior of Biological Microorganisms—An Overview

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Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules

Cited by 69 publications

References 69 publications

Angular measurements of the dynein ring reveal a stepping mechanism dependent on a flexible stalk

Angular measurements of the dynein ring reveal a stepping mechanism dependent on a flexible stalk

Atomic‐Level Coupled Interfaces and Lattice Distortion on CuS/NiS2 Nanocrystals Boost Oxygen Catalysis for Flexible Zn‐Air Batteries

Colloidal Active Matter Mimics the Behavior of Biological Microorganisms—An Overview

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Atomic‐Level Coupled Interfaces and Lattice Distortion on CuS/NiS₂ Nanocrystals Boost Oxygen Catalysis for Flexible Zn‐Air Batteries