一個(gè)包括英國(guó)利茲大學(xué)的國(guó)際性科研團(tuán)隊(duì)近日?qǐng)?bào)到了與“動(dòng)力蛋白（Dynein）”相關(guān)的新內(nèi)容,，首次識(shí)別了動(dòng)力蛋白結(jié)構(gòu)的主要元素及其運(yùn)作的絞車(chē)式機(jī)制,。該蛋白屬于馬達(dá)蛋白,，一般認(rèn)為其與神經(jīng)性紊亂有關(guān)，如運(yùn)動(dòng)神經(jīng)元病,。研究結(jié)果已經(jīng)發(fā)表于2月6日期Cell 上,。
動(dòng)力蛋白是馬達(dá)蛋白三大家庭中了解最少的一種蛋白，然而其在諸多重要生理過(guò)程中發(fā)揮關(guān)鍵作用,，如促進(jìn)精子卵子的運(yùn)動(dòng)和輔助細(xì)胞分裂等,，同時(shí)還參與細(xì)胞如運(yùn)動(dòng)神經(jīng)元內(nèi)分子物質(zhì)的運(yùn)輸。
動(dòng)力蛋白可以負(fù)載相關(guān)物質(zhì)在人體內(nèi)移動(dòng)一米的距離,，相當(dāng)于人自己徒步走40 公里之遙,。利茲大學(xué)研究團(tuán)共與其日本同事合作研究了合成肌動(dòng)蛋白，并在馬達(dá)內(nèi)部標(biāo)有熒光識(shí)別蛋白,。采用電鏡技術(shù),，他們可以對(duì)這些識(shí)別蛋白進(jìn)行定位。來(lái)自利茲大學(xué)生物科學(xué)系的首席研究員Stan Burgess 博士表示,，運(yùn)動(dòng)神經(jīng)元具有一套很復(fù)雜的轉(zhuǎn)運(yùn)系統(tǒng),。雖然運(yùn)動(dòng)神經(jīng)細(xì)胞核位于脊髓內(nèi)，但其具有穿過(guò)從脊椎到腳趾整個(gè)肢體的突觸。這類突觸是分子馬達(dá),，如動(dòng)力蛋白的“高速高路”,，一旦發(fā)生“交通事故”，將會(huì)引起細(xì)胞死亡,，最后導(dǎo)致機(jī)體肌肉萎縮,，典型的表現(xiàn)為運(yùn)動(dòng)神經(jīng)系統(tǒng)疾病。
Burgess 博士指出,，與其它蛋白質(zhì)一樣,，動(dòng)力蛋白也具有一個(gè)由長(zhǎng)線型的分子折疊而成的復(fù)雜三級(jí)空間結(jié)構(gòu)，雖然不能采用電鏡技術(shù)探明其電子結(jié)構(gòu),，但是最新的研究可以促進(jìn)研究該蛋白質(zhì)的關(guān)鍵位點(diǎn),，探明其運(yùn)動(dòng)機(jī)理。但日本的科學(xué)家認(rèn)為,，該動(dòng)力蛋白的核心與細(xì)胞內(nèi)的其它環(huán)狀分子裝置很相似,，推測(cè)其間存在著一定的進(jìn)化關(guān)系。
Burgess 博士稱,，雖其研究團(tuán)隊(duì)對(duì)于動(dòng)力蛋白結(jié)構(gòu)的認(rèn)識(shí)上還存在著一定的分歧,，但是其運(yùn)動(dòng)機(jī)制和核心結(jié)構(gòu)的發(fā)現(xiàn)，可以為以后相關(guān)科學(xué)研究提供了研究方向,。通過(guò)對(duì)動(dòng)力蛋白結(jié)構(gòu)和其運(yùn)動(dòng)機(jī)理的研究,，研究人員期望可以了解其在細(xì)胞中功能，進(jìn)而得知當(dāng)其遭到破壞時(shí)的機(jī)體的反應(yīng),。 （生物谷Bioon.com）
生物谷推薦原始出處：
Cell, Volume 136, Issue 3, 485-495, 6 February 2009 doi:10.1016/j.cell.2008.11.049
AAA+ Ring and Linker Swing Mechanism in the Dynein Motor
Anthony J. Roberts1,Naoki Numata2,Matt L. Walker3,Yusuke S. Kato1,Bara Malkova1,Takahide Kon2,Reiko Ohkura2,Fumio Arisaka4,Peter J. Knight1,Kazuo Sutoh2,,andStan A. Burgess1,,
1 Astbury Centre for Structural Molecular Biology and Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK
2 Department of Life Sciences, Graduate School of Arts and Sciences, University of Tokyo, Komaba 3-8-1, Tokyo 153-8902, Japan
3 MLW Consulting, 11 Race Hill, Launceston, Cornwall PL15 9BB, UK
4 Graduate School and School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Yokohama 226-8501, Japan
Summary
Dynein ATPases power diverse microtubule-based motilities. Each dynein motor domain comprises a ring-like head containing six AAA+ modules and N- and C-terminal regions, together with a stalk that binds microtubules. How these subdomains are arranged and generate force remains poorly understood. Here, using electron microscopy and image processing of tagged and truncated Dictyostelium cytoplasmic dynein constructs, we show that the heart of the motor is a hexameric ring of AAA+ modules, with the stalk emerging opposite the primary ATPase site (AAA1). The C-terminal region is not an integral part of the ring but spans between AAA6 and near the stalk base. The N-terminal region includes a lever-like linker whose N terminus swings by 17 nm during the ATPase cycle between AAA2 and the stalk base. Together with evidence of stalk tilting, which may communicate changes in microtubule binding affinity, these findings suggest a model for dynein's structure and mechanism.
