Molecular genetics of myosin.
Molecular genetics of myosin.
复制标题
肌球蛋白的分子遗传学。
DOI：
10.1146/annurev.bi.56.070187.003403
复制
发表时间：
1987
影响因子：
16.6
通讯作者：
Bernstein,SI
中科院分区：
文献类型：
--
作者：
EmersonJr,CP;Bernstein,SI
肌球蛋白是一种复杂的多聚蛋白，在真核生物的收缩过程中发挥着核心作用。自大约 50 年前发现以来 (1, 2)，生化研究使人们对肌肉和非肌肉细胞中肌球蛋白的结构和组织及其在收缩过程中的结构和酶功能有了详细的了解。肌球蛋白结构和功能的这些方面已得到广泛综述 (3-7, 7a)。在过去的五年里，编码肌球蛋白重链（MHC）亚基以及碱金属（alkali MLC）和调节（MLC-2）轻链亚基的基因已被克隆。这些基因的结构提供了关于无脊椎动物和脊椎动物中的肌球蛋白以及专门的肌肉和非肌肉细胞的肌球蛋白亚型的初级序列数据的极大扩展。来自进化差异生物体的肌球蛋白的比较数据有助于确定 MHC 和 MLC 蛋白的重要结构和功能域。 MHC 基因分析提供了第一个完整的 MHC 蛋白一级序列。肌球蛋白基因的克隆还导致了对由肌球蛋白基因转录本的选择性 RNA 剪接和肌球蛋白基因家族成员的表达产生的 MHC 和 MLC 蛋白亚型多样性的分子遗传学理解。肌球蛋白基因已被定位到特定的染色体位点，导致特定肌肉功能障碍的 MHC 基因突变已在果蝇（果蝇）和线虫（秀丽隐杆线虫）的 DNA 水平上得到表征。克隆的大鼠 MLC-2 基因已通过转基因方式引入小鼠胚胎中，以鉴定肌肉特异性转录调控元件，并且鸡 MLC-2 cDNA 已在体外发生突变，以鉴定 MLC-2 蛋白中的特定功能域。 在本文中，我们回顾了肌球蛋白分子遗传学的最新进展。读者还可以参考线虫 MHC 基因克隆 (8) 和碱性 MLC 基因 (9) 的最新评论。我们尝试对 MHC 基因、碱性 MLC 基因和调节性 MLC-2 基因的分子遗传学进行总体概述，强调分子遗传学对我们理解肌球蛋白的生物化学及其收缩功能、肌球蛋白基因和基因家族的进化以及肌球蛋白基因的遗传、发育和生理调节的贡献。
Myosin is a complex multimeric protein that has a central role in contractile processes of eukaryotes. Since its discovery about 50 years ago (1, 2), biochemical studies have provided a detailed understanding of the structure and organization of myosin in muscle and nonmuscle cells and its structural and enzymatic functions in contractile processes. These aspects of myosin protein structure and function have been reviewed extensively (3-7, 7a). Within the past five years, genes encoding the heavy chain (MHC) subunit and the alkali (alkali MLC) and regulatory (MLC-2) light chain subunits of myosin have been cloned. The structures of these genes have provided a greatly expanded body of primary sequence data on myosin proteins in invertebrates and vertebrates and on myosin isoforms of specialized muscle and non muscle cells. Comparative data on myosin proteins from evolutionari ly divergent organisms have contributed towards defining important structural and functional domains of MHC and MLC proteins. MHC gene analysis has provided the first complete primary sequences of MHC proteins. The cloning of myosin genes also has led to a molecular genetic understanding of the diversity of MHC and MLC protein isoforms generated by alternative RNA splicing of myosin gene transcripts and by the expression of members of myosin gene families. Myosin genes have been mapped to specific chromo somal loci, and mutations of MHC genes that cause specific muscle dysfunc tions have been characterized at the DNA level in the fruit fly, Drosophila melanogaster, and in the nematode, Caenorhabditis elegans. Cloned rat MLC-2 genes have been introduced transgenically into mouse embryos to identify muscle-specific transcriptional regulatory elements, and a chicken MLC-2 cDNA has been mutated in vitro to identify specific functional domains in the MLC-2 protein.In this article we review recent progress in the molecular genetics of myosin. The reader is also referred to recent reviews on nematode MHC gene cloning (8) and the alkali MLC genes (9). We have attempted a general overview of the molecular genetics of MHC genes, alkali MLC genes, and regulatory MLC-2 genes, emphasizing the contributions of molecular genetics to our understanding of the biochemistry of myosin and its function in contraction, the evolution of myosin genes and gene families, and the genetic, developmental, and physiological regulation of myosin genes.