4byf | pdb_00004byf
Crystal structure of human Myosin 1c in complex with calmodulin in the pre-power stroke state
Structural highlights
Function[MYO1C_HUMAN] Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments. Involved in glucose transporter recycling in response to insulin by regulating movement of intracellular GLUT4-containing vesicles to the plasma membrane. Component of the hair cell's (the sensory cells of the inner ear) adaptation-motor complex. Acts as a mediator of adaptation of mechanoelectrical transduction in stereocilia of vestibular hair cells. Binds phosphoinositides and links the actin cytoskeleton to cellular membranes (By similarity). Isoform 3 is involved in regulation of transcription. Associated with transcriptional active ribosomal genes. Appears to cooperate with the WICH chromatin-remodeling complex to facilitate transcription. Necessary for the formation of the first phosphodiester bond during transcription initiation (By similarity). Publication Abstract from PubMedMyosin 1c plays a key role in supporting motile events that underlie cell migration, vesicle trafficking, insulin-stimulated 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 beta-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 14-3-3beta (KD =0.9muM) and present the model of a double-headed myosin 1c-14-3-3 complex. This complex has been implicated in the exocytosis of GLUT4 storage vesicles during insulin-stimulated glucose uptake. Crystal Structure of Human Myosin 1c - The Motor in GLUT4 Exocytosis: Implications for Ca-Regulation and 14-3-3 Binding.,Stefan Munnich MH, Manstein DJ J Mol Biol. 2014 Mar 14. pii: S0022-2836(14)00128-4. doi:, 10.1016/j.jmb.2014.03.004. PMID:24636949[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||||
