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Münnich, S., Taft, M.H. and Manstein, D.J. (2014), Abstract

Stefan Münnich, Manuel H. Taft and Dietmar J. Manstein (2014)

Crystal Structure of Human Myosin 1c - The Motor in GLUT4 Exocytosis: Implications for Ca2+-Regulation and 14-3-3 binding.

J Mol Biol, DOI: 10.1016/j.jmb.2014.03.004



Myosin 1c plays a key role in supporting motile events that underlie cell migration, vesicle trafficking, glucose uptake and hearing. Here, we present the crystal structure of the human myosin 1c motor in complex with its light chain calmodulin. Our structure reveals tight interactions of the motor domain with calmodulin bound to the first IQ motif in the neck region. Several of the calmodulin residues contributing to this interaction are also involved in Ca2+-binding. Contact residues in the motor domain are linked to the central b-sheet and the HO helix, suggesting a mechanism for communicating changes in Ca2+-binding in the neck region to the actin and nucleotide binding regions of the motor domain. The structural context and the chemical environment of myosin 1c mutations that are involved in sensorineural hearing loss in humans are described and their impact on motor function is discussed. We show that a construct consisting of the motor domain of myosin 1c and the first IQ motif is sufficient to establish a tight interaction with 14-3-3b (KD =0.9 µM) and present the model of a double-headed myosin 1c-14-3-3 complex, which is thought to correspond to the active motor that drives exocytosis of GLUT4 storage vesicles during insulin-stimulated glucose uptake.


  • Crystal structure of human myosin 1c in the pre-power stroke state
  • Visualization of calmodulin/motor domain interactions
  • Chemical environment of myosin 1c mutations involved in hearing loss
  • Docking of myosin 1c to 14-3-3 suggests the formation of a double-headed motor