Energy Transformation in Biological Molecular Motors Alexander Vologodskii What is the molecule mechanism of transforming the energy of ATP hydrolysis into directed motion? 1. Macroscopic example of a motor action 2. Motion without inertia 3. Allosteric transitions and rectified diffusion 4. Kinetic consideration 5. Experimental data Contraction of the skeletal muscle The skeletal muscle cell Contraction of the skeletal muscle Myofibrils consist of myosin and actin filaments Contraction of the skeletal muscle Myosin filament Displacement of the myosin head The major fuel in molecular motors is ATP How a molecular motor could transform the energy of ATP hydrolysis into directed motion? Considering this question we have to take into account that there is no inertia in this scale in a liquid Let us consider motion of a bead in water There are two major ideas in the theory of molecular motors The first idea is a key role of rectified thermal diffusion The idea in this context was pioneered by Huxley in 1957 The second idea is the allosteric transitions in proteins Before binding the ligand A x1 B x2 x x2 x After binding the ligand x1 Example of the allosteric transition in protein Mowbray SL, Cole LB. 1.7 A X-ray structure of the periplasmic ribose receptor from Escherichia coli. J Mol Biol 1992;225:155–75. Bjorkman AJ, Mowbray SL. Multiple open forms of ribose-binding protein trace the path of its conformational change. J Mol Biol 1998;279:651–64. Changing of the free energy potential on ribose binding Ravindranathan KP, Gallicchio E, Levy RM. Conformational equilibria and free energy profiles for the allosteric transition of the ribosebinding protein. J Mol Biol 2005;353:196–210. Explain how the two ideas create the theory of energy transformation Diagram of the myosin head cycle Can diffusion provide the needed speed of the muscle contraction? A single cycle of a myosin head takes 0.1 – 30 ms. The rate of allosteric transitions in proteins is about 104 s-1 Is there experimental data supporting this theory? τ = τ0exp(-Fd/kT) It is possible to measure how the rate depends on the drugging force Thank you for attention
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