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Identification of muscle specific ring finger proteins as potentialregulators of the titin kinase domain

机译:鉴定肌肉特异性无名指蛋白作为titin激酶结构域的潜在调节剂

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摘要

The giant myofibrillar protein titin contains within its C-terminal region a serine-threonine kinase of unknown function. We have identified a novel muscle specific RING finger protein, referred to as MURF-1, that binds in vitro to the titin repeats A168/A169 adjacent to the titin kinase domain. Ln myofibrils, MURF-1 is present within the periphery of the M-line lattice in close proximity to titin's catalytic kinase domain, within the Z-line lattice, and also in soluble form within the cytoplasm. Yeast two-hybrid screens with MURF-1 as a bait identified two other highly homologous MURF proteins, MURF-2 and MURF-3. MURF-1,2,3 proteins are encoded by distinct genes, share highly conserved N-terminal RING domains and in vitro form dimers/heterodimers by shared coiled-coil motifs. Of the MURF family, only MURF-1 interacts with titin repeats A168/A169, whereas MURF-3 has been reported to affect microtubule stability. Association of MURF-1 with M-line titin may potentially modulate titin's kinase activity similar to other known kinase-associated proteins, whereas differential expression and heterodimerization of MURF1, 2 and 3 may link together titin kinase and microtubule-dependent signal pathways in striated muscles.
机译:巨大的肌原纤维蛋白效价蛋白在其C端区域内含有功能未知的丝氨酸-苏氨酸激酶。我们已经确定了一种新型的肌肉特异性RING指蛋白,称为MURF-1,它在体外与与titin激酶结构域相邻的titin重复序列A168 / A169结合。在肌原纤维中,MURF-1存在于M线晶格的外围,紧靠titin的催化激酶结构域,存在于Z线晶格,并且以可溶形式存在于细胞质中。以MURF-1为诱饵的酵母双杂交筛选确定了另外两种高度同源的MURF蛋白,即MURF-2和MURF-3。 MURF-1,2,3蛋白由不同的基因编码,共享高度保守的N端RING域,并通过共享的卷曲螺旋基序在体外形成二聚体/异二聚体。在MURF家族中,只有MURF-1与titin重复序列A168 / A169相互作用,而据报道MURF-3会影响微管的稳定性。与其他已知的激酶相关蛋白相似,MURF-1与M-line titin的结合可能潜在地调节titin的激酶活性,而MURF1、2和3的差异表达和异二聚化可能将条纹肌中的titin激酶和微管依赖性信号通路联系在一起。

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