Mutations at the same amino acid in myosin that cause either skeletal or cardiac myopathy have distinct molecular phenotypes.
Mutations at the same amino acid in myosin that cause either skeletal or cardiac myopathy have distinct molecular phenotypes.
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DOI：
10.1016/j.yjmcc.2009.10.011
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发表时间：
2010-05
影响因子：
5
通讯作者：
Leinwand LA
中科院分区：
文献类型：
--
作者：
Armel TZ;Leinwand LA
To date, more than 230 disease causing mutations have been linked to the slow/cardiac muscle myosin gene, β-MyHC (MYH7). The majority of these mutations are located in the globular head region of the protein and result in cardiomyopathies. Recently, however, a number of novel disease causing mutations have been described in the long, α-helical, coiled-coil tail region of the β-MyHC protein. Mutations in this region are of particular interest because they are associated with a multitude of human diseases, including both cardiac and skeletal myopathies. Here, we attempt to dissect the mechanism(s) by which mutations in the rod region of β-MyHC can cause a variety of diseases by analyzing two mutations at a single amino acid (R1500P and R1500W) which cause two distinct diseases (Laing-type early onset distal myopathy and dilated cardiomyopathy, respectively). For diseases linked to the R1500 residue, we find that each mutation displays distinct structural, thermodynamic, and functional properties. Both R1500P and R1500W cause a decrease in thermodynamic stability, though the R1500W phenotype is more severe. Both mutations also affect filament assembly, with R1500P causing an additional decrease in filament stability. In addition to furthering our understanding of the mechanism of pathogenesis for each of these diseases, these data also suggest how the variance in molecular phenotype may be associated with the variance in clinical phenotype present with mutations in the β-MyHC rod.
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影响因子：
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作者：
Sinard, J H;Stafford, W F;Pollard, T D
通讯作者：
Pollard, T D
影响因子：
18.2
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Greenfield, Norma J.
DOI：
10.1073/pnas.0900107106
发表时间：
2009-04-14
影响因子：
11.1
作者：
Armel, Thomas Z.;Leinwand, Leslie A.
通讯作者：
Leinwand, Leslie A.