小小的一段蛋白質是如何讓細胞走路?


How Tiny Cell Proteins Generate Force To 'Walk'



ScienceDaily (Dec. 4, 2008) — 來自麻省理工學院(MIT)的研究人員發現如何透過蛋白質所發揮的力量來產生運動,而這樣的運動可以在細胞分裂當中被發現。



圖1. Kinesin, a small motor protein found in cells, walks stepwise on microtubules to perform cellular processes. In each step, a power stroke is generated when two mechanical elements (neck linker, in red, and cover strand, in blue) form a beta-sheet that folds to drive the protein forward.


Kinesin 是一種運動蛋白(motor protein),這種蛋白質同時也是神經傳導物質的攜帶者,而且它會沿著微管(microtubules)「行走」。透過 MIT 的團隊讓人們首次瞭解在分子層次上的 kinesin 是如何產生沿著微管行走的力量。



圖2. The kinesin dimer attaches to, and moves along, microtubules.(圖片來源:http://en.wikipedia.org/wiki/Kinesin


本研究是由 Matthew Lang 所率領,他是生物及機械工程的副教授,而這項研究已經發表在 11月 24 日出版的美國國家科學院報(Proceedings of the National Academy of Sciences,簡稱 PNAS)期刊上。



圖3. Mechanical and biological engineering professor Matthew Lang, left, and graduate student David Appleyard in the lab.(圖片來源:http://web.mit.edu/newsoffice/2007/nano-assembly-1031.html


由於 kinesin 也參與了細胞分裂的組織機制過程,因此瞭解這個蛋白質是如何運作對於開發出與細胞行為失控的相關疾病而言便顯得相當重要,細胞失控最為人所知的疾病便是癌症。

這個蛋白質包含了兩個「頭部」,這個頭部可以沿著微管行走,它並帶有一個長長的「尾巴」,這個尾巴的功用在承載貨物。當頭部沿著微管行走時,他最快的時速可達每秒 100 步,大概是 800 奈米(nanometers)的距離。



圖4. In this video, a bead has been loaded with a single kinesin molecule. When the bead comes in contact with a microtubule polymer (the thin rod), the kinesin motor runs unidirectionally on the microtubule polymer at a velocity of 600 - 1000 nm/sec.(影像來源:http://techtv.mit.edu/videos/1342-cell-protein-walking


發表在 PNAS 期刊中,Lang 與他的同事們提出了實驗的證據來輔佐發表在 1 月份 Structure 期刊中的模型結果。他們的模型提出 ─ 以及新的實驗證據 ─ 接合著頭部與尾部的一小塊蛋白質會對 kinesin 行走時所製造的力量產生回應。兩個蛋白質的次單元,也就是 N-端(N-terminal)覆蓋股及頸部鏈結會彼此相互串連而形成一個摺狀(sheet),而這個摺狀則會形成 cover-neck 束(cover-neck bundle)來驅動 kinesin 朝頭部前進。



圖5. Model for kinesin’s power stroke. (A) Before ATP binding, the NL (red) and N-terminal CS (blue, thick S-shaped tube) of the leading motor head are rendered out-of-register by the unwound portion (green, thick tube) of alpha 6 (magenta). (B) ATP binding results in retraction of alpha 4 (yellow), allowing the extra helical turn of alpha 6 to form and bringing the NL and CS into a favorable position to form a beta-sheet, known as the CNB. (C) The CNB possesses the forward bias to deliver a power stroke and propel the trailing head forward. After this action, the new leading head searches for its next MT binding site in a poststroke confined space, and the C-terminal half of the NL latches onto the motor head, achieving its final, ""docked"" position. Kinesin dimers were constructed by using PDB 1MKJ (with CNB) and PDB 1BG2 (without CNB). The neck coiled-coil stalk was extended based on PDB 3KIN. (D) Diagram model highlighting the major molecular events that lead to CNB formation and a
power stroke.


Lang 說到:「這就是 kinesin 的能量來源。」

接下來,Lang 的團隊計畫研究兩個 kinesin 的頭部是怎麼彼此通訊來完成它們的步伐。

本研究還包含了機械工程的研究生 Ahmad Khalil。而其他 MIT 的作者則包含了生物工程的研究生 David Appleyard;最近從 MIT 畢業的 Anna Labno,以及最近來 Lang 實驗室的拜訪學生 Adrien Georges。Angela Belcher, the Germehausen Professor of Materials Science and Engineering and Biological Engineering. This work is a close collaboration with authors Martin Karplus of Harvard and Wonmuk Hwang of Texas A&M.

The research was funded by the National Institutes of Health and the Army Research Office Institute of Collaborative Biotechnologies.


Adapted from materials provided by Massachusetts Institute of Technology.


原始論文:
Kinesin's cover-neck bundle folds forward to generate force
PNAS published online before print December 1, 2008
doi:10.1073/pnas.0805147105

本篇論文是 OPEN ACCESS ARTICLE 唷!意思就是大家都可以看,沒有鎖!有興趣的朋友快去下載來看看吧~


原始報導:
ScienceDaily:How Tiny Cell Proteins Generate Force To 'Walk'


相關報導:
MIT NEWS:http://web.mit.edu/newsoffice/2008/cell-motor-1124.html