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Cell Mol Life Sci. 2012 Jan;69(2):299-311. doi: 10.1007/s00018-011-0749-8. Epub 2011 Jun 18.

Functional characterization of the human myosin-7a motor domain.

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  • 1Institut für Biophysikalische Chemie, Medizinische Hochschule Hannover, Hannover, Germany.


Myosin-7a participates in auditory and visual processes. Defects in MYO7A, the gene encoding the myosin-7a heavy chain, are causative for Usher syndrome 1B, the most frequent cause of deaf-blindness in humans. In the present study, we performed a detailed kinetic and functional characterization of the isolated human myosin-7a motor domain to elucidate the details of chemomechanical coupling and the regulation of motor function. A rate-limiting, slow ADP release step causes long lifetimes of strong actin-binding intermediates and results in a high duty ratio. Moreover, our results reveal a Mg(2+)-sensitive regulatory mechanism tuning the kinetic and mechanical properties of the myosin-7a motor domain. We obtained direct evidence that changes in the concentration of free Mg(2+) ions affect the motor properties of human myosin-7a using an in vitro motility assay system. Our results suggest that in a cellular environment, compartment-specific fluctuations in free Mg(2+) ions can mediate the conditional switching of myosin-7a between cargo moving and tension bearing modes.

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