期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 282, 期 47, 页码 34276-34287出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M703267200
关键词
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资金
- NIEHS NIH HHS [P01 ES 11188] Funding Source: Medline
Three mutations (R120G, Q151X, and 464delCT) in the small heat shock protein alpha B-crystallin cause inherited myofibrillar myopathy. In an effort to elucidate the molecular basis for the associated myopathy, we have determined the following for these mutant alpha B-crystallin proteins: (i) the formation of aggregates in transfected cells; (ii) the partition into different subcellular fractions; (iii) the phosphorylation status; and (iv) the ability to interact with themselves, with wild-type alpha B-crystallin, and with other small heat shock proteins that are abundant in muscles. We found that all three alpha B-crystallin mutants have an increased tendency to form cytoplasmic aggregates in transfected cells and significantly increased levels of phosphorylation when compared with the wildtype protein. Although wild-type alpha B-crystallin partitioned essentially into the cytosol and membranes/organelles fractions, mutant alpha B-crystallin proteins partitioned additionally into the nuclear and cytoskeletal fractions. By using various protein interaction assays, including quantitative fluorescence resonance energy transfer measurements in live cells, we found abnormal interactions of the various alpha B-crystallin mutants with wild-type alpha B-crystallin, with themselves, and with the other small heat shock proteins Hsp20, Hsp22, and possibly with Hsp27. The collected data suggest that each alpha B-crystallin mutant has a unique pattern of abnormal interaction properties. These distinct properties of the alpha B-crystallin mutants identified are likely to contribute to a better understanding of the gradual manifestation and clinical heterogeneity of the associated myopathy in patients.
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