Ménétrey Julie, Bahloul Amel, Wells Amber L, Yengo Christopher M, Morris Carl A, Sweeney H Lee, Houdusse Anne
Structural Motility, Institut Curie CNRS, UMR144, 26 rue d'Ulm, 75248 Paris cedex 05, France.
Nature. 2005 Jun 9;435(7043):779-85. doi: 10.1038/nature03592.
Here we solve a 2.4-A structure of a truncated version of the reverse-direction myosin motor, myosin VI, that contains the motor domain and binding sites for two calmodulin molecules. The structure reveals only minor differences in the motor domain from that in plus-end directed myosins, with the exception of two unique inserts. The first is near the nucleotide-binding pocket and alters the rates of nucleotide association and dissociation. The second unique insert forms an integral part of the myosin VI converter domain along with a calmodulin bound to a novel target motif within the insert. This serves to redirect the effective 'lever arm' of myosin VI, which includes a second calmodulin bound to an 'IQ motif', towards the pointed (minus) end of the actin filament. This repositioning largely accounts for the reverse directionality of this class of myosin motors. We propose a model incorporating a kinesin-like uncoupling/docking mechanism to provide a full explanation of the movements of myosin VI.
在此，我们解析了反向肌球蛋白马达（肌球蛋白VI）截短版本的2.4埃结构，该截短版本包含马达结构域以及两个钙调蛋白分子的结合位点。该结构显示，除了两个独特的插入序列外，马达结构域与正向肌球蛋白的马达结构域仅有细微差异。第一个插入序列靠近核苷酸结合口袋，改变了核苷酸结合和解离的速率。第二个独特插入序列与结合在该插入序列内一个新靶基序上的钙调蛋白一起，构成了肌球蛋白VI转换结构域的一个组成部分。这使得肌球蛋白VI的有效“杠杆臂”（包括结合在一个“IQ基序”上的第二个钙调蛋白）转向肌动蛋白丝的尖端（负）端。这种重新定位在很大程度上解释了这类肌球蛋白马达的反向运动特性。我们提出了一个包含类似驱动蛋白的解偶联/对接机制的模型，以全面解释肌球蛋白VI的运动。
