Biology subjects

Takaki, R.

Publications and source records attributed to Takaki, R..

3 recordsLinked to original sources

bioRxiv2022

Structural changes in chromosomes driven by multiple condensin motors during mitosis

We created a computational framework that describes the loop extrusion (LE) by multiple condensin I and II motors in order to investigate the changes in chromosome organization during mitosis. The theory accurately reproduces the experimentally measured contact probability profiles for the mitotic chromosomes in HeLa and DT40 cells. The rate of loop extrusion is smaller at the start of mitosis and increases as the cells approach the metaphase. The mean loop size generated by condensin II is about six times larger than the ones created by condensin I. The loops, which overlap with each other, are stapled to a central dynamically changing helical scaffold formed by the motors during the LE process. The structures of the mitotic chromosomes, using a data-driven method that uses the Hi-C contact map as input, are best described as random helix perversion (RHP) in which the handedness changes randomly along the scaffold. The extent of propagation in the RHP structures is less in HeLa cells than in the DT40 chromosomes.

biophysics↗

bioRxiv2021

Information flow, Gating, and Energetics in dimeric molecular motors

Molecular motors belonging to the kinesin and myosin super family hydrolyze ATP by cycling through a sequence of chemical states. These cytoplasmic motors are dimers made up of two linked identical monomeric globular proteins. Fueled by the free energy generated by ATP hydrolysis, the motors walk on polar tracks (microtubule or filamentous actin) processively, which means that only one head detaches and executes a mechanical step while the other stays bound to the track. Thus, the one motor head must regulate chemical state of the other, referred to as "gating", a concept that is not fully understood. Inspired by experiments, showing that only a fraction of the energy from ATP hydrolysis is used to advance the kinesin motors against load, we demonstrate that additional energy is used for coordinating the chemical cycles of the two heads in the dimer - a feature that characterizes gating. To this end, we develop a general framework based on information theory and stochastic thermodynamics, and establish that gating could be quantified in terms of information flow between the motor heads. Applications of the theory to kinesin-1 and Myosin V show that information flow occurs, with positive cooperativity, at external resistive loads that are less than a critical value, Fc. When force exceeds Fc, effective information flow ceases. Interestingly, Fc, which is independent of the input energy generated through ATP hydrolysis, coincides with force at which the probability of backward steps starts to increase. Our findings suggest that transport efficiency is optimal only at forces less than Fc, which implies that these motors must operate at low loads under in vivo conditions.

biophysics↗

bioRxiv2020

On the theory of condensin mediated loop extrusion in genomes

Condensation of hundreds of mega-base-pair-long human chromosomes in a small nuclear volume is a spectacular biological phenomenon. This process is driven by the formation of chromosome loops. The ATP consuming motor, condensin, interacts with chromatin segments to actively extrude loops. Motivated by real-time imaging of loop extrusion (LE), we created an analytically solvable model, predicting the LE velocity and step size distribution as a function of external load. The theory fits the available experimental data quantitatively, and suggests that condensin must undergo a large conformational change, induced by ATP binding, bringing distant parts of the motor to proximity. Simulations using a simple model confirm that the motor transitions between an open and a closed state in order to extrude loops by a scrunching mechanism, similar to that proposed in DNA bubble formation during bacterial transcription. Changes in the orientation of the motor domains are transmitted over ~ 50 nm, connecting the motor head and the hinge, thus providing an allosteric basis for LE.

biophysics↗