JAWAHARLAL NEHRU UNIVERSITY
SCHOOL OF COMPUTATIONAL AND INTEGRATIVE SCIENCES
S E M I N A R
Speaker: Dr. Sabeeha Hasnain
Title: Crowding modulates the stepping dynamics of Kinesin
Date 22-06-2018
Time 3.30pm
Venue Seminar room, SCIS, JNU
Abstract
Kinesins are dimeric motor proteins which move along the Microtubule (MT) and transport cargo like cellular organelles, mRNA and signaling molecules towards the cell periphery. Macromolecular crowding inside the cell is likely to play a key role in modulating the stepping dynamics of kinesin owing to volume exclusion effects. We will present Brownian dynamics simulation results, using the Self-Organized Polymer model of the Kinesin-Microtubule complex developed by Zhang and Thirumalai [1] in the presence of spherical crowders. We find that the docking of the neck-linker, a key event in driving the stepping process, is unaffected by the crowding agents. In contrast, the diffusive motion of the trailing head (TH), which covers the majority of the 16 nm step [2], is greatly impeded due to crowding. Moreover, crowders decrease the lateral displacement of the trailing head (TH), thus confining stepping the TH diffusion to the central protofilament of the microtubule (MT). The effect is most apparent at a high concentration of crowders, when excluded volume effects hinder the motion of TH. This results in a reduced distance between the free and bound kinesin head, resulting in a stochastic motion of the TH along the MT. We relate our findings to the experiments of Conway and Ross [3], which showed in-vitro the reversal of kinesin motion in a crowded environment.
References:
[1] Zhang Z, Thirumalai D (2012) Dissecting the kinematics of the kinesin step. Structure 20:628-640.
[2] Zhang Z, Goltzvik Y, Thirumalai D (2017) Parsing the roles of neck-linker docking and tethered head diffusion in the stepping dynamics of kinesin. Proc. Natl. Acad. Sci USA. E9838-E9845.
[3] Conway L, Ross J L (2014) Kinesin Motor Transport is Altered by Macromolecular Crowding and Transiently Associated Microtubule-Associated Proteins. arXiv :1409.3455.
