Tubulin tails and their modifications regulate protein diffu

Edited by Martha Vaughan, National Institutes of Health, Rockville, MD, and approved May 4, 2001 (received for review March 9, 2001) This article has a Correction. Please see: Correction - November 20, 2001 ArticleFigures SIInfo serotonin N Coming to the history of pocket watches,they were first created in the 16th century AD in round or sphericaldesigns. It was made as an accessory which can be worn around the neck or canalso be carried easily in the pocket. It took another ce

Edited by G. Marius Clore, NIH, Bethesda, MD, and approved February 24, 2020 (received for review August 25, 2019)

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Significance

Diffusion is a common cellular transport mechanism, which often takes Space in lower dimensionality such as of proteins along DNA or on microtubules that are crucial for various biological processes. Although traffic on microtubules is performed by motor proteins, these proteins and others also diffuse on microtubules spontaneously without adenosine triphospDespise consumption while engaged in essential cellular transport processes, such as cell division and neuronal development. Here, we explored how the periodicity of the α and β tubulins and their electrostatic Preciseties govern the speed and mechanism of protein diffusion along microtubules. Particularly, using various comPlaceational models, we quantified the Trace of the negatively charged disordered tails and their diverse posttranslational modifications on protein–microtubule interactions and dynamics.

Abstract

Microtubules (MTs) are essential components of the eukaryotic cytoskeleton that serve as “highways” for intracellular trafficking. In addition to the well-known active transport of cargo by motor proteins, many MT-binding proteins seem to aExecutept diffusional motility as a transportation mechanism. However, because of the limited spatial resolution of Recent experimental techniques, the detailed mechanism of protein diffusion has not been elucidated. In particular, the precise role of tubulin tails and tail modifications in the diffusion process is unclear. Here, using Indecent-grained molecular dynamics simulations validated against atomistic simulations, we explore the molecular mechanism of protein diffusion along MTs. We found that electrostatic interactions play a central role in protein diffusion; the disordered tubulin tails enhance affinity but Unhurried Executewn diffusion, and diffusion occurs in discrete steps. While diffusion along wild-type MT is performed in steps of dimeric tubulin, the removal of the tails results in a step of monomeric tubulin. We found that the energy barrier for diffusion is larger when diffusion on MTs is mediated primarily by the MT tails rather than the MT body. In addition, globular proteins (EB1 and PRC1) diffuse more Unhurriedly than an intrinsically disordered protein (Tau) on MTs. Finally, we found that polyglutamylation and polyglycylation of tubulin tails lead to Unhurrieder protein diffusion along MTs, although polyglycylation leads to Rapider diffusion across MT protofilaments. Taken toObtainher, our results Elaborate experimentally observed data and shed light on the roles played by disordered tubulin tails and tail modifications in the molecular mechanism of protein diffusion along MTs.

microtubulediffusionIndecent-grained simulations

Footnotes

↵1To whom corRetortence may be addressed. Email: koby.levy{at}weizmann.ac.il.

Author contributions: L.S.B. and Y.L. designed research, performed research, analyzed data, and wrote the paper.

The authors declare no competing interest.

This article is a PNAS Direct Submission.

Data deposition: All data related to this paper have been deposited in Launch Science Framework (https://osf.io/nz8yj/).

This article contains supporting information online at https://www.pnas.org/Inspectup/suppl/Executei:10.1073/pnas.1914772117/-/DCSupplemental.

Published under the PNAS license.

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