Structure of androcam supports specialized interactions with myosin VI.
Structure of androcam supports specialized interactions with myosin VI.
复制标题
androcam 的结构支持与肌球蛋白 VI 的专门相互作用。
DOI：
10.1073/pnas.1209730109
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发表时间：
2012
影响因子：
11.1
通讯作者：
MacKenzie,KevinR
中科院分区：
文献类型：
--
作者：
Joshi,MehulK;Moran,Sean;Beckingham,KathleenM;MacKenzie,KevinR
Androcam取代钙调素作为一个组织特异性肌球蛋白VI轻链上的肌动蛋白锥介导D。黑腹精细胞个体化我们发现，androcam结构和其结合的肌球蛋白VI结构（插入2）和监管（IQ）轻链网站是不同的钙调蛋白，并提供了专门的肌球蛋白VI功能的基础。androcam的N叶非规范地结合一个单一的Ca 2+，并被锁定在一个“封闭”的构象，导致androcam接触插入2网站与其C叶只。Androcam在插入物2处取代钙调蛋白将增加肌球蛋白VI杠杆臂的灵活性，这可能有利于肌球蛋白VI的紧凑单体形式，其通过促进C-末端区域塌陷到运动域上而在肌动蛋白锥上起作用。拴系的androcam N叶可以通过与马达的C-末端部分接触来稳定单体，或者将其他成分招募到肌动蛋白锥中。Androcam在所有钙水平下都与IQ位点结合，在组成上模仿钙调蛋白仅在中等钙水平下采用的构象。因此，androcam取代钙调蛋白在智商将废除钙2+调节，钙调蛋白介导的肌球蛋白VI结构的变化。我们建议，N叶防止androcam干扰其他钙调素介导的Ca 2+信号转导事件。我们讨论了如何选择性地稳定钙调素的许多构象之一的基因复制和突变，支持结构和功能不同的钙调素样蛋白的分子进化。
Androcam replaces calmodulin as a tissue-specific myosin VI light chain on the actin cones that mediateD. melanogasterspermatid individualization. We show that the androcam structure and its binding to the myosin VI structural (Insert 2) and regulatory (IQ) light chain sites are distinct from those of calmodulin and provide a basis for specialized myosin VI function. The androcam N lobe noncanonically binds a single Ca2+and is locked in a “closed” conformation, causing androcam to contact the Insert 2 site with its C lobe only. Androcam replacing calmodulin at Insert 2 will increase myosin VI lever arm flexibility, which may favor the compact monomeric form of myosin VI that functions on the actin cones by facilitating the collapse of the C-terminal region onto the motor domain. The tethered androcam N lobe could stabilize the monomer through contacts with C-terminal portions of the motor or recruit other components to the actin cones. Androcam binds the IQ site at all calcium levels, constitutively mimicking a conformation adopted by calmodulin only at intermediate calcium levels. Thus, androcam replacing calmodulin at IQ will abolish a Ca2+-regulated, calmodulin-mediated myosin VI structural change. We propose that the N lobe prevents androcam from interfering with other calmodulin-mediated Ca2+signaling events. We discuss how gene duplication and mutations that selectively stabilize one of the many conformations available to calmodulin support the molecular evolution of structurally and functionally distinct calmodulin-like proteins.