Mechanistic basis for motor-driven membrane constriction by dynamin

Item Type:	Preprint
Title:	Mechanistic basis for motor-driven membrane constriction by dynamin
Creators Name:	Ganichkin, O. and Vancraenenbroeck, R. and Rosenblum, G. and Hofmann, H. and Mikhailov, A.S. and Daumke, O. and Noel, J.K.
Abstract:	The mechano-chemical GTPase dynamin assembles on membrane necks of clathrin-coated vesicles into helical oligomers that constrict and eventually cleave the necks in a GTP-dependent way. It remains not clear whether dynamin achieves this via molecular motor activity and, if so, by what mechanism. Here, we used ensemble kinetics, single-molecule FRET and molecular dynamics simulations to characterize dynamin’s GTPase cycle and determine the powerstroke strength. The results were incorporated into a coarse-grained structural model of dynamin filaments on realistic membrane templates. Working asynchronously, dynamin’s motor modules were found to collectively constrict a membrane tube. Force is generated by motor dimers linking adjacent helical turns and constriction is accelerated by their strain-dependent dissociation. Consistent with experiments, less than a second is needed to constrict a membrane tube to the hemi-fission radius. Thus, a membrane remodeling mechanism relying on cooperation of molecular ratchet motors driven by GTP hydrolysis has been revealed.
Source:	bioRxiv
Publisher:	Cold Spring Harbor Laboratory Press
Article Number:	2020.09.10.289546
Date:	11 September 2020
Official Publication:	https://doi.org/10.1101/2020.09.10.289546

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