Myo1c mutations associated with hearing loss cause defects in the interaction with nucleotide and actin.

Adamek, Nancy and Geeves, Michael A. and Coluccio, Lynne M. (2011) Myo1c mutations associated with hearing loss cause defects in the interaction with nucleotide and actin. Cellular and Molecular Life Sciences, 68 (1). pp. 139-150. ISSN 1420-9071. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1007/s00018-010-0448-x

Abstract

Three heterozygous missense mutations in the motor domain of myosin 1c (Myo1c), which mediates adaptation in the inner ear, are associated with bilateral sensorineural hearing loss in humans. With transient kinetic analyses, steady-state ATPase and motility assays, and homology modeling, we studied the interaction of these mutants with nucleotide and actin using a truncated construct, Myo1c(1IQ-SAH), which includes an artificial lever arm. Results indicate that mutation R156W, near switch 1, affects the nucleotide-binding pocket and the calcium binding by disrupting switch 1 movement. Mutation V252A, in the K helix of the upper 50 kDa domain, showed reduced actin affinity consistent with disruption of communication between the actin- and nucleotide-binding sites. T380M, in a Myo1c-specific insert in the HO linker, displayed aberrant changes in most kinetic parameters and uncoupling of the ATPase from motility. These data allow for an interpretation of how these mutations might affect adaptation.

Item Type: Article
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Sue Davies
Date Deposited: 03 Nov 2011 12:11
Last Modified: 16 Apr 2014 13:34
Resource URI: http://kar.kent.ac.uk/id/eprint/28339 (The current URI for this page, for reference purposes)
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