The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss.
The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss.
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DOI：
10.1098/rsob.140107
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发表时间：
2014-07
期刊：
影响因子：
5.8
通讯作者：
Choi JY
中科院分区：
文献类型：
--
作者：
Kwon TJ;Oh SK;Park HJ;Sato O;Venselaar H;Choi SY;Kim S;Lee KY;Bok J;Lee SH;Vriend G;Ikebe M;Kim UK;Choi JY
五种非常规肌球蛋白基因的突变与遗传性听力损失（HL）有关。这些基因编码马达蛋白肌球蛋白IA、IIIA、VI、VIIA和XVA。迄今为止，大多数肌球蛋白基因突变已被发现在高加索人群。此外，只有少数功能研究已进行了先前报道的肌球蛋白突变。我们对韩国常染色体显性遗传非综合征型HL病例的MYO1A和MYO6基因突变进行了筛查和功能研究。我们在MYO6中发现了四种新的杂合突变。三个突变（p.R825X、p.R991X和Q918fsX941）产生肌球蛋白VI蛋白的过早截短。另一个突变，p.R205Q，在体外分析中与肌动蛋白激活的ATP酶活性和肌球蛋白VI的肌动蛋白滑行速度降低有关。这一发现与蛋白质建模研究的结果一致，并证实了MYO6基因中这种突变的致病性。在MYO1A基因中发现了一个错义变体p.R544W，计算机分析表明该变体对蛋白质功能具有有害影响。这一发现与蛋白质建模研究的结果一致，并证实了MYO6基因中这种突变的致病作用。
Mutations in five unconventional myosin genes have been associated with genetic hearing loss (HL). These genes encode the motor proteins myosin IA, IIIA, VI, VIIA and XVA. To date, most mutations in myosin genes have been found in the Caucasian population. In addition, only a few functional studies have been performed on the previously reported myosin mutations. We performed screening and functional studies for mutations in the MYO1A and MYO6 genes in Korean cases of autosomal dominant non-syndromic HL. We identified four novel heterozygous mutations in MYO6. Three mutations (p.R825X, p.R991X and Q918fsX941) produce a premature truncation of the myosin VI protein. Another mutation, p.R205Q, was associated with diminished actin-activated ATPase activity and actin gliding velocity of myosin VI in an in vitro analysis. This finding is consistent with the results of protein modelling studies and corroborates the pathogenicity of this mutation in the MYO6 gene. One missense variant, p.R544W, was found in the MYO1A gene, and in silico analysis suggested that this variant has deleterious effects on protein function. This finding is consistent with the results of protein modelling studies and corroborates the pathogenic effect of this mutation in the MYO6 gene.
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影响因子：
2.8
作者：
Oonk, A. M. M.;Leijendeckers, J. M.;Pennings, R. J. E.
通讯作者：
Pennings, R. J. E.
DOI：
10.1083/jcb.137.6.1287
发表时间：
1997-06-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hasson T;Gillespie PG;Garcia JA;MacDonald RB;Zhao Y;Yee AG;Mooseker MS;Corey DP
通讯作者：
Corey DP
影响因子：
9.8
作者：
Ahmed, ZM;Morell, RJ;Wilcox, ER
通讯作者：
Wilcox, ER
影响因子：
3.3
作者：
Berg, JS;Powell, BC;Cheney, RE
通讯作者：
Cheney, RE
影响因子：
7.5
作者：
CHENEY R E;MOOSEKER M S
通讯作者：
MOOSEKER M S