Myo1c mutations associated with hearing loss cause defects in the interaction with nucleotide and actin.
Myo1c mutations associated with hearing loss cause defects in the interaction with nucleotide and actin.
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与听力损失相关的myo1c突变导致与核苷酸和肌动蛋白相互作用的缺陷。
DOI：
10.1007/s00018-010-0448-x
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发表时间：
2011-01
影响因子：
8
通讯作者：
Coluccio, Lynne M.
中科院分区：
文献类型：
--
作者：
Adamek, Nancy;Geeves, Michael A.;Coluccio, Lynne M.
肌球蛋白1c(Myo1c)运动域的三个杂合性错义突变(Myo1c)介导内耳的适应，与人类双侧感音神经性听力损失有关。通过瞬时动力学分析、稳态ATPase和运动分析以及同源模型，我们使用包含人工杠杆臂的截断结构Myo1c1IQ-SAH研究了这些突变体与核苷酸和肌动蛋白的相互作用。结果表明，位于开关1附近的突变R156W通过破坏开关1的运动来影响核苷酸结合口袋和钙结合。位于上50 kDa结构域K螺旋的突变V252a显示，肌动蛋白亲和力降低，与肌动蛋白和核苷酸结合位点之间的通讯中断一致。在HO连接子的Myo1c特异性插入片段中，T380M表现出大多数动力学参数的异常变化和ATPase与运动的解偶联。这些数据可以解释这些突变可能如何影响适应。
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, Myo1c1IQ-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.
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影响因子：
64.5
作者：
Gillespie PG;Müller U
通讯作者：
Müller U
影响因子：
21.3
作者：
Murphy, CT;Rock, RS;Spudich, JA
通讯作者：
Spudich, JA
影响因子：
11.4
作者：
Kintses, Balint;Gyimesi, Mates;Malnasi-Csizmadia, Andras
通讯作者：
Malnasi-Csizmadia, Andras
影响因子：
2.9
作者：
Málnási-Csizmadia, A;Pearson, DS;Bagshaw, CR
通讯作者：
Bagshaw, CR
影响因子：
2.9
作者：
Málnási-Csizmadia, A;Woolley, RJ;Bagshaw, CR
通讯作者：
Bagshaw, CR