Hongyun Wang's Research on Molecular Motors

Movie Movie

The above are cartoon animations of F1 motor and Fo motor of the ATP synthase.
Click here for more movies of the ATP synthase.

Hongyun Wang's research in biophysics and molecular modeling is to investigate the mechanism by which chemical energy is converted into mechanical work in biological systems. Cells store chemical energy in two forms: as transmembrane electrochemical gradients and in chemical bonds, particularly the gamma phosphate bond in adenosine triphosphate (ATP). ATP is the most important chemical energy source in all living cells. In mitochondria, bacteria, and chloroplasts the free energy stored in transmembrane electrochemical gradients is used to synthesize ATP from ADP and phosphate via the membrane-bound enzyme ATP synthase. ATP synthase can also reverse itself and hydrolyze ATP to pump ions against an electrochemical gradient. ATP synthase consists of two portions: a membrane-spanning portion, Fo, comprising the ion channel, and a soluble portion, F1, containing three catalytic sites (see the Figure below). Both Fo and F1 are reversible rotary motors --- perhaps the smallest motors known to science. Fo uses the transmembrane electrochemical gradient to generate a rotary torque to drive ATP synthesis in F1 or, when driven backwards by the torque generated in F1, to pump ions uphill against their transmembrane electrochemical gradient. F1 generates a rotary torque by hydrolyzing ATP at its three catalytic sites or, when turned backwards by the torque generated in Fo, as a synthesizer of ATP.

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Working with George Oster's group at UC Berkeley, Hongyun Wang constructed separate models for the Fo and F1 portions of ATP synthase which explained how the energy is transduced from the transmembrane electrochemical gradient to a mechanical torque in Fo (see Refs [1] and [3] ), and how the energy is transduced from ATP to a mechanical torque in F1 (see Refs [2], [4], [5] and [6]). These are the first quantitative models of this enzyme, and are in good agreement with the existing experiments.

In carrying out this research Hongyun Wang developed a computer program to deduce the kinematic motions of the F1 motor from John Walker's crystal structure of F1. Some of the results and animation movies were included in the interactive CD of the book "Essential Cell Biology" by Alberts, et al. All animation movies can be accessed at http://www.cnr.berkeley.edu/~hongwang/Project/ATP_synthase.

Hongyun Wang's recent research is focused on how the free energy liberated in the ATP hydrolysis cycle is converted efficiently to generate a force. The binding zipper model was proposed to explain the high efficiency of the F1 motor (see Refs [5] and [6]):

The binding zipper model
In the hydrolysis direction, an ATP in solution first diffuses to the catalytic site and is weakly bound (ATP docking). The rate of this step is affected by the ATP concentration in solution. The weakly bound ATP may dissociate from the catalytic site, returning to the solution. Occasionally, it proceeds from weak binding to tight binding (the binding transition). During the binding transition, the bonds between the ATP and the catalytic site form sequentially, ATP binding affinity increases gradually, and each bond formation drives a small conformational change. In this way, the binding free energy is used efficiently to generate a nearly constant force during the multi-step ATP binding transition. ATP concentration in solution does not affect the binding transition, but only how often ATP attempts docking to the catalytic site. After the binding transition, the ATP is in chemical equilibrium with ADP and Pi. The transition ATP <--> ADP + Pi weakens the ATP binding and distributes it over ADP and Pi so that the hydrolysis products can be released and the cycle repeated.

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This project is supported by NSF.