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2012年諾貝爾化學(xué)獎Robert J. Lefkowitz和Brian K. Kobilka
Robert J. Lefkowitz來自杜克大學(xué)，Brian K. Kobilka來自斯坦福大學(xué)。因發(fā)現(xiàn)G蛋白歐聯(lián)受體研究而獲獎。

你的身體是一個精妙調(diào)和的系統(tǒng)，幾十億細(xì)胞之間相互作用。每一個細(xì)胞都具有微小的受體，使其可以感知周圍環(huán)境，以適應(yīng)新情況。羅伯特·萊夫科維茨和布萊恩·克比爾卡被授予2012年諾貝爾化學(xué)獎，因?yàn)樗麄兊耐黄菩园l(fā)現(xiàn)揭示了這種受體的一個重要家族：G蛋白偶聯(lián)受體的內(nèi)部工作機(jī)理。

長期以來，人們并不清楚細(xì)胞如何感知周圍環(huán)境?？茖W(xué)家知道腎上腺素等激素可以發(fā)揮強(qiáng)大的作用：提高血壓，加快心跳。他們懷疑細(xì)胞表面存在某種激素的接收器。但是這些接收器究竟由什么組成、如何工作，在20世紀(jì)大部分時間里仍然是一個未解之謎。

Lefkowitz在1968年開始利用放射性方法追蹤細(xì)胞受體。他將同位素碘連接在多種激素分子上，在輻射的作用下，他得以發(fā)現(xiàn)若干種受體，其中包括一種腎上腺素受體：β腎上腺素受體。他的團(tuán)隊(duì)從細(xì)胞膜中分離出了隱藏其中的受體，并初步得出了它們的工作機(jī)制。

團(tuán)隊(duì)在1980年代取得了進(jìn)一步的突破。后來招進(jìn)的Kobilka接受了從龐大的人類基因組中分離編碼β腎上腺素受體基因的挑戰(zhàn)。他具有創(chuàng)造性的方法使他達(dá)成了目標(biāo)。當(dāng)研究者們分析這一基因是，他們發(fā)現(xiàn)這一受體與眼中的一個感光受體相似。他們意識到存在一個受體家族，它們彼此結(jié)構(gòu)類似，而且以相同的方式產(chǎn)生功能。

今天這個蛋白家族被稱為G蛋白偶聯(lián)受體，大約1000個基因?yàn)檫@些受體編碼；這些受體涵蓋了光線、嗅覺、味覺、腎上腺素、組胺、多巴胺還有五羥色胺等多個領(lǐng)域。所有藥物里大約一半是通過G蛋白偶聯(lián)受體發(fā)揮作用的。

團(tuán)隊(duì)在1980年代取得了進(jìn)一步的突破。后來招進(jìn)的Kobilka接受了從龐大的人類基因組中分離編碼β腎上腺素受體基因的挑戰(zhàn)。他具有創(chuàng)造性的方法使他達(dá)成了目標(biāo)。當(dāng)研究者們分析這一基因是，他們發(fā)現(xiàn)這一受體與眼中的一個感光受體相似。他們意識到存在一個受體家族，它們彼此結(jié)構(gòu)類似，而且以相同的方式產(chǎn)生功能。

Lefkowitz and Kobilka 的研究對于理解G蛋白偶聯(lián)受體發(fā)揮作用的方式至關(guān)重要。特別是2011年，Kobilka
又取得了另一項(xiàng)重大突破：他和他的研究組捕捉到了β-腎上腺素受體被激素激活、向細(xì)胞發(fā)送信號的那一瞬間的景象。這幅圖片本身就是分子尺度的大師之作——是數(shù)十年研究的結(jié)晶。
 

10 October 2012

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry for 2012 to

Robert J. Lefkowitz
Howard Hughes Medical Institute and Duke University Medical Center, Durham, NC, USA

and

Brian K. Kobilka
Stanford University School of Medicine, Stanford, CA, USA

"for studies of G-protein–coupled receptors"

Smart receptors on cell surfaces

Your body is a fine-tuned system of interactions between billions of cells. Each cell has tiny receptors that enable it to sense its environment, so it can adapt to new situtations. Robert Lefkowitz and Brian Kobilka are awarded the 2012 Nobel Prize in Chemistry for groundbreaking discoveries that reveal the inner workings of an important family of such receptors: G-protein–coupled receptors.

For a long time, it remained a mystery how cells could sense their environment. Scientists knew that hormones such as adrenalin had powerful effects: increasing blood pressure and making the heart beat faster. They suspected that cell surfaces contained some kind of recipient for hormones. But what these receptors actually consisted of and how they worked remained obscured for most of the 20th Century.

Lefkowitz started to use radioactivity in 1968 in order to trace cells' receptors. He attached an iodine isotope to various hormones, and thanks to the radiation, he managed to unveil several receptors, among those a receptor for adrenalin: β-adrenergic receptor. His team of researchers extracted the receptor from its hiding place in the cell wall and gained an initial understanding of how it works.

The team achieved its next big step during the 1980s. The newly recruited Kobilka accepted the challenge to isolate the gene that codes for the β-adrenergic receptor from the gigantic human genome. His creative approach allowed him to attain his goal. When the researchers analyzed the gene, they discovered that the receptor was similar to one in the eye that captures light. They realized that there is a whole family of receptors that look alike and function in the same manner.

Today this family is referred to as G-protein–coupled receptors. About a thousand genes code for such receptors, for example, for light, flavour, odour, adrenalin, histamine, dopamine and serotonin. About half of all medications achieve their effect through G-protein–coupled receptors.

The studies by Lefkowitz and Kobilka are crucial for understanding how G-protein–coupled receptors function. Furthermore, in 2011, Kobilka achieved another break-through; he and his research team captured an image of the β-adrenergic receptor at the exact moment that it is activated by a hormone and sends a signal into the cell. This image is a molecular masterpiece – the result of decades of research.