Structure：驱动蛋白产生动力的根源

Wonmuk Hwang etc.…

驱动蛋白的一个根本性的问题是：三磷酸腺苷（ATP）是通过何种机制结合来生成运动所需的动力？

在最新的研究中，Hwang等人通过分析现有结构，并加以分子动力学模拟研究发现，颈部连接器的构象变化的涉及了9个残基的N端区域，即肽链，这是产生动力不可或缺的力量。

研究表明，在结合三磷酸腺苷之前，驱动蛋白与颈部连接器形成了一个β片，即颈部束，从而诱发颈部连接器向前运动，随后通过插销式的结合运动到头部。另外，对运动停止的估算和模型的各向异性外部荷载的计算结果都与测量出的挟制力数据完全一致。

此外，Hwang等提出的通过形成颈部束的方式产生动力的可能适用于多个驱动蛋白族。新的研究阐明了驱动蛋白作为目前已知的最小的动力马达的设计原理。

相关论文发表在2008年1月8日的《结构》（Structure）杂志上。（科学网武彦文/编译）

（《结构》（Structure），Vol 16, 62-71, 08 January 2008，Wonmuk Hwang, Martin Karplus）

生物谷推荐原始出处：

Structure, Vol 16, 62-71, 08 January 2008

Article

Force Generation in Kinesin Hinges on Cover-Neck Bundle Formation

Wonmuk Hwang,1, Matthew J. Lang,2 and Martin Karplus3,4,

1 Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA
2 Department of Biological Engineering & Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
3 Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA
4 Laboratoire de Chimie Biophysique, ISIS Université Louis Pasteur, 67000 Strasbourg, France

Corresponding author
Martin Karplus
marci@tammy.harvard.edu

Corresponding author
Wonmuk Hwang
hwm@tamu.edu

In kinesin motors, a fundamental question concerns the mechanism by which ATP binding generates the force required for walking. Analysis of available structures combined with molecular dynamics simulations demonstrates that the conformational change of the neck linker involves the nine-residue-long N-terminal region, the cover strand, as an element that is essential for force generation. Upon ATP binding, it forms a β sheet with the neck linker, the cover-neck bundle, which induces the forward motion of the neck linker, followed by a latch-type binding to the motor head. The estimated stall force and anisotropic response to external loads calculated from the model agree with force-clamp measurements. The proposed mechanism for force generation by the cover-neck bundle formation appears to apply to several kinesin families. It also elucidates the design principle of kinesin as the smallest known processive motor.