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She1 affects dynein through direct interactions with the microtubule and the dynein microtubule-binding domain.

ABSTRACT: Cytoplasmic dynein is an enormous minus end-directed microtubule motor. Rather than existing as bare tracks, microtubules are bound by numerous microtubule-associated proteins (MAPs) that have the capacity to affect various cellular functions, including motor-mediated transport. One such MAP is She1, a dynein effector that polarizes dynein-mediated spindle movements in budding yeast. Here, we characterize the molecular basis by which She1 affects dynein, providing the first such insight into which a MAP can modulate motor motility. We find that She1 affects the ATPase rate, microtubule-binding affinity, and stepping behavior of dynein, and that microtubule binding by She1 is required for its effects on dynein motility. Moreover, we find that She1 directly contacts the microtubule-binding domain of dynein, and that their interaction is sensitive to the nucleotide-bound state of the motor. Our data support a model in which simultaneous interactions between the microtubule and dynein enables She1 to directly affect dynein motility.

SUBMITTER: Ecklund KH

PROVIDER: S-EPMC5732302 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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She1 affects dynein through direct interactions with the microtubule and the dynein microtubule-binding domain.

Ecklund Kari H KH Morisaki Tatsuya T Lammers Lindsay G LG Marzo Matthew G MG Stasevich Timothy J TJ Markus Steven M SM

Nature communications 20171215 1

Cytoplasmic dynein is an enormous minus end-directed microtubule motor. Rather than existing as bare tracks, microtubules are bound by numerous microtubule-associated proteins (MAPs) that have the capacity to affect various cellular functions, including motor-mediated transport. One such MAP is She1, a dynein effector that polarizes dynein-mediated spindle movements in budding yeast. Here, we characterize the molecular basis by which She1 affects dynein, providing the first such insight into whi ...[more]

PMID: 29247176

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Project description:This study compares the role of electrostatics in the binding process between microtubules and two dynein microtubule-binding domains (MTBDs): cytoplasmic and axonemal. These two dyneins are distinctively different in terms of their functionalities: cytoplasmic dynein is processive, while axonemal dynein is involved in beating. In both cases, the binding requires frequent association/disassociation between the microtubule and MTBD, and involves highly negatively charged microtubules, including non-structured C-terminal domains (E-hooks), and an MTBD interface that is positively charged. This indicates that electrostatics play an important role in the association process. Here, we show that the cytoplasmic MTBD binds electrostatically tighter to microtubules than to the axonemal MTBD, but the axonemal MTBD experiences interactions with microtubule E-hooks at longer distances compared with the cytoplasmic MTBD. This allows the axonemal MTBD to be weakly bound to the microtubule, while at the same time acting onto the microtubule via the flexible E-hooks, even at MTBD⁻microtubule distances of 45 Å. In part, this is due to the charge distribution of MTBDs: in the cytoplasmic MTBD, the positive charges are concentrated at the binding interface with the microtubule, while in the axonemal MTBD, they are more distributed over the entire structure, allowing E-hooks to interact at longer distances. The dissimilarities of electrostatics in the cases of axonemal and cytoplasmic MTBDs were found not to result in a difference in conformational dynamics on MTBDs, while causing differences in the conformational states of E-hooks. The E-hooks' conformations in the presence of the axonemal MTBD were less restricted than in the presence of the cytoplasmic MTBD. In parallel with the differences, the common effect was found that the structural fluctuations of MTBDs decrease as either the number of contacts with E-hooks increases or the distance to the microtubule decreases.

Dataset Information

She1 affects dynein through direct interactions with the microtubule and the dynein microtubule-binding domain.

Publications

She1 affects dynein through direct interactions with the microtubule and the dynein microtubule-binding domain.

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