驅(qū)動(dòng)蛋白的一個(gè)根本性的問題是：三磷酸腺苷（ATP）是通過何種機(jī)制結(jié)合來生成運(yùn)動(dòng)所需的動(dòng)力,？
在最新的研究中,，Hwang等人通過分析現(xiàn)有結(jié)構(gòu)，并加以分子動(dòng)力學(xué)模擬研究發(fā)現(xiàn),，頸部連接器的構(gòu)象變化的涉及了9個(gè)殘基的N端區(qū)域,，即肽鏈,，這是產(chǎn)生動(dòng)力不可或缺的力量。
研究表明,，在結(jié)合三磷酸腺苷之前,，驅(qū)動(dòng)蛋白與頸部連接器形成了一個(gè)β片，即頸部束,，從而誘發(fā)頸部連接器向前運(yùn)動(dòng),，隨后通過插銷式的結(jié)合運(yùn)動(dòng)到頭部。另外,，對(duì)運(yùn)動(dòng)停止的估算和模型的各向異性外部荷載的計(jì)算結(jié)果都與測(cè)量出的挾制力數(shù)據(jù)完全一致,。
此外，Hwang等提出的通過形成頸部束的方式產(chǎn)生動(dòng)力的可能適用于多個(gè)驅(qū)動(dòng)蛋白族,。新的研究闡明了驅(qū)動(dòng)蛋白作為目前已知的最小的動(dòng)力馬達(dá)的設(shè)計(jì)原理,。
相關(guān)論文發(fā)表在2008年1月8日的《結(jié)構(gòu)》（Structure）雜志上。（科學(xué)網(wǎng) 武彥文/編譯）
（《結(jié)構(gòu)》（Structure）,，Vol 16, 62-71, 08 January 2008,，Wonmuk Hwang, Martin Karplus）
生物谷推薦原始出處：
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
[email protected]
Corresponding author
Wonmuk Hwang
[email protected]
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.
