Functional diversity between orthologous myosins with minimal sequence diversity
Functional diversity between orthologous myosins with minimal sequence diversity
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DOI：
10.1023/a:1005640004495
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发表时间：
2000-05-01
影响因子：
2.7
通讯作者：
Reggiani, C
中科院分区：
文献类型：
--
作者：
Canepari, M;Rossi, R;Reggiani, C
为了定义导致直系同源肌节肌球蛋白之间功能多样性的结构差异，我们比较了大鼠和人类β/慢肌球蛋白。功能比较表明，与人β/慢肌球蛋白相比，大鼠β/慢肌球蛋白具有更高的ATP酶活性，并且在体外运动测定中以更高的速度移动肌动蛋白丝。序列分析表明，25 和 50 kDa 结构域（环 1）以及 50 和 20 kDa 结构域（环 2）连接处的环区域（与确定肌球蛋白重链的功能多样性有关）在两个直向同源物中基本相同。两条肌球蛋白重链中只有 14 个非保守取代，其中 3 个位于次级肌动蛋白结合环和侧翼区域，其他取代对应于迄今为止尚未指定功能作用的残基，包括近端 S2 结构域中的两个残基。有趣的是，在其中一些位置，大鼠β/慢速肌球蛋白重链具有与人类心脏α肌球蛋白、快速型肌球蛋白和快速骨骼肌球蛋白中发现的相同残基。这些观察结果表明，具有有限序列多样性的肌球蛋白直向同源物的功能和结构分析可以提供有用的线索来鉴定参与调节肌球蛋白功能的氨基酸残基。
To define the structural differences that are responsible for the functional diversity between orthologous sarcomeric myosins, we compared the rat and human beta/slow myosins. Functional comparison showed that rat beta/slow myosin has higher ATPase activity and moves actin filaments at higher speed in in vitro motility assay than human beta/slow myosin. Sequence analysis shows that the loop regions at the junctions of the 25 and 50 kDa domains (loop 1) and the 50 and 20 kDa domains (loop 2), which have been implicated in determining functional diversity of myosin heavy chains, are essentially identical in the two orthologs. There are only 14 non-conservative substitutions in the two myosin heavy chains, three of which are located in the secondary actin-binding loop and flanking regions and others correspond to residues so far not assigned a functional role, including two residues in the proximal S2 domain. Interestingly, in some of these positions the rat beta/slow myosin heavy chain has the same residues found in human cardiac alpha myosin, a fast-type myosin, and fast skeletal myosins. These observations indicate that functional and structural analysis of myosin orthologs with limited sequence diversity can provide useful clues to identify amino acid residues involved in modulating myosin function.