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因对“G蛋白偶联受体研究”两位美国科学家获得2012年诺贝尔化学奖

因对“G蛋白偶联受体研究”两位美国科学家获得2012年诺贝尔化学奖

北京时间10月10日下午5点45分,2012年诺贝尔化学奖揭晓,两位美国科学家罗伯特·莱夫科维茨(Robert J. Lefkowitz)和布莱恩·克比尔卡(Brian K. Kobilka)因“G蛋白偶联受体研究”获奖。二人将均分800万瑞典克朗奖金。

罗伯特·莱夫科维茨(Robert J. Lefkowitz),美国公民。1943年出生于美国纽约。1966年从纽约哥伦比亚大学获得MD。美国霍华德·休斯医学研究所研究人员,美国杜克大学医学中心医学教授、生物化学教授。

布莱恩·克比尔卡(Brian K. Kobilka),美国公民。1955年出生于美国明尼苏达州Little Falls。1981年从耶鲁大学医学院获得MD。斯坦福大学医学院医学教授、分子与细胞生理学教授。(克比尔卡《科学》文章: G蛋白偶联受体“停靠站”结构被确定)(《自然》特写文章报道克比尔卡)

细胞表面的聪明受体

每个人的身体就是一个数十亿细胞相互作用的精确校准系统。每个细胞都含有微小的受体,可让细胞感知周围环境以适应新状态。罗伯特·莱夫科维茨和布莱恩·克比尔卡因为突破性地揭示G蛋白偶联受体这一重要受体家族的内在工作机制而获得2012年诺贝尔化学奖。

长期以来,细胞如何感知周围环境一直是一个未解之谜。科学家已经弄清像肾上腺素这样的激素所具有的强大效果:提高血压、让心跳加速。他们猜测,细胞表面可能存在某些激素受体。但在上个世纪大部分时期里,这些激素受体的实际成分及其工作原理却一直是未知数。

莱夫科维茨于1968年开始利用放射学来追踪细胞受体。他将碘同位素附着到各种激素上,借助放射学,成功找到数种受体,其中一种便是肾上腺素的受体:β-肾上腺素受体。他的研究小组将这种受体从细胞壁的隐蔽处抽出并对其工作原理有了初步认识。

研究团队在1980年代取得了下一步重要进展。新加入的克比尔卡开始挑战难题,意欲将编码β-肾上腺素受体的基因从浩瀚的人类基因组中分离出来。他的创造性方法帮助他实现了目标。当研究人员分析该基因时,他们发现该受体与眼中捕获光的受体相类似。他们认识到,存在着一整个家族看起来相似的受体,而且起作用的方式也一样。

今天这一家族被称作“G蛋白偶联受体”。大约一千个基因编码这类受体,适用于光、味道、气味、肾上腺素、组胺、多巴胺以及复合胺等。大约一半的药物通过G蛋白偶联受体起作用。

莱夫科维茨和克比尔卡的研究对于理解G蛋白偶联受体如何起作用至关重要。此外,在2011年,克比尔卡还取得了另一项突破:他和研究团队在一个精确的时刻——β-肾上腺素受体被激素激活并向细胞发送信号——获得了β-肾上腺素受体图像。这一图像是一个分子杰作,可谓几十年辛苦研究的成果。

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诺贝尔奖网站官方公告(英文)

Press Release

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.

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Robert J. Lefkowitz, U.S. citizen. Born 1943 in New York, NY, USA. M.D. 1966 from Columbia University, New York, NY, USA.Investigator, Howard Hughes Medical Institute. James B. Duke Professor of Medicine, and Professor of Biochemistry, Duke University Medical Center, Durham, NC, USA.
www.lefkolab.org

Brian K. Kobilka, U.S. citizen. Born 1955 in Little Falls, MN, USA. M.D. 1981 from Yale University School of Medicine, New Haven, CT, USA. Professor of Medicine, and Professor of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.
http://med.stanford.edu/kobilkalab

 

The Prize amount: SEK 8 million, to be shared equally between the Laureates.
Contacts: Erik Huss, Press Officer, phone +46 8 673 95 44, +46 70 673 96 50,erik.huss@kva.se
Ann Fernholm, Editor, Phone +46 70 750 22 16, ann.fernholm@kva.se

The Royal Swedish Academy of Sciences, founded in 1739, is an independent organization whose overall objective is to promote the sciences and strengthen their influence in society. The Academy takes special responsibility for the natural sciences and mathematics, but endeavours to promote the exchange of ideas between various disciplins.


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