RT Journal Article
SR Electronic
T1 Regulatory mechanisms of the dynein-2 motility by post-translational modification revealed by MD simulation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.17.480877
DO 10.1101/2022.02.17.480877
A1 Shintaroh Kubo
A1 Khanh Huy Bui
YR 2022
UL http://biorxiv.org/content/early/2022/02/19/2022.02.17.480877.abstract
AB Intraflagellar transport for ciliary assembly and maintenance is driven by dynein and kinesins specific for the cilia. It has been shown that anterograde and retrograde transports run on different regions of the doublet microtubule, i.e., separate train tracks. However, little is known about the regulatory mechanism of this selective process. Since the doublet microtubule is known to display specific post-translational modifications of tubulins, i.e. “tubulin code”, for molecular motor regulations, we investigated the motility of ciliary specific dynein-2 under different post-translational modification by coarse-grained molecular dynamics. Our setup allows us to simulate the stochastic stepping behaviors of dynein-2 on un-modified, detyrosinated, poly-glutamylated and poly-glycylated microtubules in silico. Our study revealed that poly-glutamylation can play an inhibitory effect on dynein-2 motility. Our result indicates that poly-glutamylation of the B-tubule of the doublet microtubule can be used as an efficient means to target retrograde intraflagellar transport onto the A-tubule.Competing Interest StatementThe authors have declared no competing interest.