一組特殊的蛋白質(zhì),，即所謂的分子伴侶,，幫助其他蛋白獲得它們正確的構(gòu)象,。直到今天科學(xué)家一直認(rèn)為ATP的水解為分子伴侶Hsp90大的構(gòu)象改變提供著能量,。目前來自 慕尼黑納米系統(tǒng)研究（NIM）的研究團隊證明Hsp90利用熱波動作為構(gòu)象改變的驅(qū)動力,。研究結(jié)果發(fā)表于PNAS期刊上。
ATP是大多數(shù)有機體的主要能量來源,，ATPase是利用這種燃料的機器,，在體內(nèi)移動肌肉或貨物。伴侶蛋白Hsp90在體內(nèi)含量非常豐富,，在它2個單體蛋白中每一個單體都有一個ATPase,。過去幾年的研究顯示，ATPase蛋白的運動及構(gòu)象變化通常嚴(yán)格地與ATP的結(jié)合和水解相關(guān)聯(lián),。
為了探討這一理論,，慕尼黑工業(yè)大學(xué)（TUM）教授及NIM成員Thorsten Hugel和他的團隊設(shè)計了一種特殊的三色單分子熒光共振能量轉(zhuǎn)移（FRET）實驗和交替的激光激發(fā)（ALEX）來同時觀測ATP的結(jié)合和構(gòu)象改變,。不料,，實驗顯示，ATP的結(jié)合和水解并不與Hsp90的大構(gòu)象變化相關(guān),。相反,，Hsp90是由熱波動驅(qū)動的高度靈活的機器。
"熱波動是蛋白質(zhì)結(jié)構(gòu)的隨機變化--它們可以被認(rèn)為是與環(huán)境中水分子之間的碰撞,，在活的有機體中熱波動進行的相當(dāng)劇烈,，"Thorsten Hugel說。"利利用這些撞擊在不同的構(gòu)象之間來回切換,，節(jié)省了Hsp90寶貴的ATP",。但Hsp90伴侶的ATPase的任務(wù)是什么？科學(xué)家推測共伴侶和底物蛋白該表了系統(tǒng),，使得ATP的結(jié)合和水解能夠進行一項重要的任務(wù),。
隨著新開發(fā)的實驗裝置,，現(xiàn)在可以對這個異常復(fù)雜的系統(tǒng)進行更詳細(xì)的調(diào)查研究以解決這個重要問題。慕尼黑生物物理學(xué)家為分子機器的能量轉(zhuǎn)換提供了一個新的視角,。（生物谷bioon.com）
doi:10.1073/pnas.1107930108
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Heat shock protein 90’s mechanochemical cycle is dominated by thermal fluctuations
Christoph Ratzke, Felix Berkemeier, and Thorsten Huge
Abstract：The molecular chaperone and heat shock protein 90 (Hsp90) exists mainly as a homodimer in the cytoplasm. Each monomer has an ATPase in its N-terminal domain and undergoes large conformational changes during Hsp90’s mechanochemical cycle. The three-color single-molecule assay and data analysis presented in the following allows one to observe at the same time nucleotide binding and the conformational changes in Hsp90. Surprisingly, and completely unlike the prior investigated systems, nucleotides can bind to the N-terminally open and closed state without strictly forcing the protein into a specific conformation. Both the transitions between the conformational states and the nucleotide binding/unbinding are mainly thermally driven. Furthermore, the two ATP binding sites show negative cooperativity; i.e., nucleotides do not bind independently to the two monomers. We thus reveal a picture of how nucleotide binding and conformational changes are connected in the molecular chaperone Hsp90, which has far-ranging consequences for its function and is distinct from previously investigated motor proteins.
