Dissecting the role of the ?-subunit in the rotary-chemical coupling and torque generation of F1-ATPase.

ABSTRACT: Unraveling the molecular nature of the conversion of chemical energy (ATP hydrolysis in the ?/?-subunits) to mechanical energy and torque (rotation of the ?-subunit) in F1-ATPase is very challenging. A major part of the challenge involves understanding the rotary-chemical coupling by a nonphenomenological structure-energy description, while accounting for the observed torque generated on the ?-subunit and its change due to mutation of this unit. Here we extend our previous study that used a coarse-grained model of the F1-ATPase to generate a structure-based free energy landscape of the rotary-chemical process. Our quantitative analysis of the landscape reproduced the observed torque for the wild-type enzyme. In doing so, we found that there are several possibilities of torque generation from landscapes with various shapes and demonstrated that a downhill slope along the chemical coordinate could still result in negligible torque, due to ineffective coupling of the chemistry to the ?-subunit rotation. We then explored the relationship between the functionality and the underlying sequence through systematic examination of the effect of various parts of the ?-subunit on free energy surfaces of F1-ATPase. Furthermore, by constructing several types of ?-deletion systems and calculating the corresponding torque generation, we gained previously unknown insights into the molecular nature of the F1-ATPase rotary motor. Significantly, our results are in excellent agreement with recent experimental findings and indicate that the rotary-chemical coupling is primarily established through electrostatic effects, although specific contacts through ?-ionizable residue side chains are not essential for establishing the basic features of the coupling.

SUBMITTER: Mukherjee S 

PROVIDER: S-EPMC4352810 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature