Abstract
SMC (structural maintenance of chromosomes) protein complexes are ring-shaped molecular motors essential for genome folding. Despite recent progress, the detailed molecular mechanism of DNA translocation in concert with the ATP-driven conformational changes of the complex remains to be clarified. In this study, we elucidated the mechanisms of SMC action on DNA using all-atom and coarse-grained molecular dynamics simulations. We first created a near-atomic full-length model of a prokaryotic SMC-kleisin complex based on experimental structures and implemented ATP-dependent conformational changes using a structure-based coarse-grained model. We further incorporated key protein-DNA hydrogen bond interactions derived from fully atomistic simulations. Extensive simulations of the SMC complex with 800 base pairs of duplex DNA over the ATP cycle observed unidirectional DNA translocation by the SMC complex. The process exhibited a step size of ~200 base pairs, wherein the SMC complex captured a DNA segment of about the same size within the SMC ring in the engaged state, followed by its pumping into the kleisin ring as ATP was hydrolyzed. Analysis of trajectories identified the asymmetric path of the kleisin as a critical factor for the observed unidirectionality.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
We conducted three additional simulations (1) A control simulation with no hydrogen bonds between SMC heads and DNA. This is to test our experimentally testable prediction on the importance of specific hydrogen bonds. (2) A series of mutant simulations with prolonged ScpA (kleisin) disordered linkers. This is to test another testable prediction that the shortness of the kleisin is a key to unidirectional movement. These together provide predictions that can be examined experimentally in the future. (3) An all-atom MD simulation to identify key interactions between the SMC heads and DNA with a third set of force-fields.
