专英资料2010年诺贝尔化学奖 - 图文

The Nobel Prize in Chemistry 2012 was awarded jointly to Robert J. Lefkowitz and Brian K. Kobilka \

2012诺贝尔化学奖共同授予罗伯特J莱夫科维茨和布瑞恩K. Kobilka”为研究G蛋白偶联受体”

Brian K. Kobilka - Facts

Brian K. Kobilka 布瑞恩K. Kobilka

Born: 1955, Little Falls, MN, USA 出世：1955，小瀑布，MN，USA

Affiliation at the time of the award: Stanford University School of Medicine, Stanford, CA, USA

在颁奖时间单位：斯坦福大学医学院，斯坦福大学，加州，美国 Prize motivation: \

奖的动机：“研究G蛋白偶联受体” Field: biochemistry

领域：生物化学布莱恩·克比尔卡，著名结构生物学家，斯坦福大学医学院分子与细胞生理与医学系教授，美国国家科学院院士，以GPCRs结构生物学研究著称。

Brian Kvilca, the famous structural biologists, and Medicine Department of cell physiology professor at the Stanford University School of medicine molecular,academician of the National Academy of Sciences USA, structural biology is known for his research on GPCRs.

1955年出生于美国明尼苏达州LittleFalls。1981年从耶鲁大学医学院获得MD。2007年，Kobilka与科学家RaymondC.Stevens，利用T4溶菌酶融合蛋白方法解析了第一个非视紫红质GPCR晶体结构：人beta2肾上腺素受体，他还独立地通过抗体片段介导法解析了人beta2肾上腺素受体的结构。2011年，Kobilka研究组解析了结合激动剂的处于活性状态的人beta2肾上腺素受体的结构（Nature，2011，被引56次）。随后又解析Gαβγ-β2肾上腺素受体复合物的结构，完整解释了GPCRs如何被配体激活以及再激活下游G蛋白从而传递信号的过程。

Born in 1955 in Minnesota Prefecture America LittleFalls. 1981 MD from the Yale University School of medicine. In 2007, Kobilka and RaymondC.Stevens scientists, the use of T4 lysozyme fusion protein analysis method of the first non rhodopsin crystal structure of GPCR: beta2 adrenergic receptor, he alsoindependently by analyzing the antibody fragment mediated method to thestructure of the human beta2 adrenergic receptor. In 2011, Kobilka study on the structure of group analytic combination is active agonist human beta2adrenergic receptor (Nature, 2011, cited 56 times). The structure then parses the G alpha beta gamma beta 2 adrenergic receptor complexes, explained the whole process of how GPCRs are ligand activated and RE activated downstream of G protein to transfer signal.

2012年4月受聘清华大学客座教授。

In 2012 April to now a visiting professor at Tsinghua University.

2012年10月10日，2012年诺贝尔化学奖揭晓，两位美国科学家罗伯特·莱夫科维茨和布莱恩·克比尔卡因“G蛋白偶联受体研究”获奖。

In October 10, 2012, the Nobel prize for chemistry in 2012 announced that two American scientists Robert Lefkowitz and Brian Kabir Caine \award.

Robert J. Lefkowitz - Facts

Robert J. Lefkowitz 罗伯特J莱夫科维茨

Born: 15 April 1943, New York, NY, USA 出世：15四月1943，纽约，NY，USA

Affiliation at the time of the award: Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC, USA

在颁奖时间联系：霍华德休斯医学研究所，杜克大学医学中心，达勒姆，NC，USA Prize motivation: \奖的动机：“研究G蛋白偶联受体” Field: biochemistry 领域：生物化学

Tracking Receptors 跟踪受体

When you are afraid, your heart beats faster, your blood pressure rises, and you breathe more heavily. This is partly the result of adrenaline forming in your body, which causes your heart rate to accelerate. Adrenaline is a hormone, a substance that manages communication between the cells in your body. Each cell has a small receiver known as a receptor, which is able to receive hormones. What these receptors look like and how they work remained a mystery for many years.

当你害怕时，你的心跳会加速，你的血压上升，你呼吸的更严重。这部分是肾上腺素在你身上形成的结果，使你的心跳加速。肾上腺素是一种激素，物质管理你的身体细胞之间的通信。每个单元都有一个被称为受体的小接收器，这是能够接受激素。这些受体看起来像他们的工作保持多年的一个谜。

In order to track these receptors, in 1968 Robert Lefkowitz attached a radioactive isotope of the element iodine to different hormones. By tracking the radiation emitted by the isotope, he succeeded in finding a receptor for adrenaline, which allowed him to build an understanding of how it functions. In the 1980s, Brian Kobilka successfully identified the gene that regulates the formation of this receptor. The two researchers also discovered that the receptor was similar to receptors located in the eye that capture light. It was later discovered that there is an entire family of receptors that look and act in similar ways - known as G-protein-coupled receptors. Approximately half of all medications used today make use of this kind of receptor.

为了追踪这些受体，在1968罗伯特莱夫科维茨附加的元素碘的一种放射性同位素不同的激素。通过跟踪的同位素发射的辐射，他成功地发现了一种肾上腺素受体，这让他建立一个理解它的功能。在上世纪80年代，布瑞恩Kobilka成功识别基因调节该受体的形成。两位研究者也发现了类似的受体位于眼睛捕捉光受体。后来发现有一整个家族的受体的外观和行为以类似的方式被称为G蛋白偶联受体。大约有一半的所有药物利用今天这种受体。

想要了解G蛋白偶联受体，则必须从G蛋白说起。G蛋白是一类可以与生物小分子GDP或GTP结合，具有特征性GTP酶活性的蛋白质。在动物体内，最重要的一类是“三聚体G蛋白”——也就是1994年诺贝尔生理学或医学奖的故事。这类G蛋白是生物体内信息传递的重要媒介，可以接收上游信号，并把这些信号传递给下游的诸如腺苷酸环化酶、磷脂酶C等效应器，产生多种第二信使，并通过级联放大最终产生各种生理效应。[1] [2] [3] To understand G protein coupled receptor, it must start from the G protein. Gprotein is a kind of small biological molecules can be combined with GDP or GTP, which has the characteristic of enzyme activity of GTP protein. In animals, a class is the most important \-- the 1994 Nobel prize in physiology or medicine story. This class of G proteins are the important media of information transfer in organism, can receive the upstreamsignals, and these signals to downstream such as adenylate cyclase andphospholipase C effector, produce various second messenger, and through the cascade eventually produce physiological effect.

在信号转导的途径上，三聚体G蛋白的上游是一类具有七个跨膜区域的细胞膜受体蛋白，

它们就是G蛋白偶联受体。这些蛋白质横跨在细胞的边界——细胞膜之上，一面可以接触外面世界的信号，一面可以与细胞内部的物质发生作用，他们是细胞外信息进入细胞内的桥梁。[1] 在很多生物体中，三聚体G蛋白的三个亚基都有多种不同的形式，因而不同的组合数量繁多，相应的，这些生物体内也存在大量不同的G蛋白偶联受体。纵观人类基因组，我们拥有至少907个G蛋白偶联受体，[5] 而且这个数字还在一直变化中，目前的数据是1000个上下 [6] ——这个数量相当于人体所有编码蛋白质基因的5%。这样的数量并不惊人，毕竟在几种常见的模式动物中，简单如秀丽隐杆线虫（1149种以上），复杂如小鼠（1318种以

上），都拥有比人类数量更多的G蛋白偶联受体。[7]

In the signal transduction pathways, the upper reaches of heterotrimeric G protein is a class with seven trans membrane region of the receptor protein,they are G protein coupled receptors. These proteins across cell boundaries --on the side of cell membrane, the signal can be in contact with the outsideworld, one can and the cell's internal material occur, they are extracellularinformation into the bridge within the cell. [1] in many organisms, the three subunits of heterotrimeric G protein has many different forms, so the numberof different combinations of variety, accordingly, these organisms are also a large number of G protein coupled receptor different. Throughout the human genome, we have at least 907 G protein coupled receptors, [5] and the number is always changing, the present data are 1000 upper and lower [6] -this number is equivalent to all 5% human protein coding genes. This number is not surprising, after all, in the animal model of several common, simple asCaenorhabditis elegans (more than 1149), complex such as mice (more than 1318), more than the number of human G protein coupled receptors. [7] 虽然这些微小的蛋白质看不见摸不着，但是它们与我们的日常生活息息相关，如果没有G蛋白偶联受体，人类根本无法生存下去。如果没有视紫质，我们将看不见光线；如果没有嗅觉受体，我们将闻不见气味；如果没有β-肾上腺素受体，我们将无法调节血糖；如果没有毒蕈碱受体，乙酰胆碱将无法将心跳速度限定在合理范围内；如果没有5-羟色胺受体，我们甚至无法感受幸福??[3]

Although these small proteins are invisible and untouchable, but they and our daily life are closely related, if there is no G protein coupled receptors,humanity cannot survive. If there is no rhodopsin, we will not see the light; if there is no olfactory receptors, we don't smell smell; if no beta adrenergic receptor, we will be unable to regulate blood sugar; if there is no muscarinic receptor, acetylcholine cannot be heart rate defined in the reasonable range;If there is no 5- serotonin receptor, we even cannot feel happy...... [3]

本届诺贝尔奖得主莱夫科维茨是从上个世纪60年代末起开始相关研究的，当时研究的内容是促肾上腺皮质激素。在成功分离得到了这种重要激素的受体，并成功地解析了它的作用机制十余年之后，他所带领的研究团队第一次克隆到了编码这个受体的基因。在80年代初，克隆一个基因犹如大海捞针，而莱夫科维茨招收的博士后——也就是本届诺贝尔奖的另一位得主——科比尔卡做到了。这个基因的克隆是将他们推上诺贝尔奖得主宝座的关键，因为他们很快发现这种受体的结构与之前发现的光受体视紫质有些许类似

The Nobel award winner Lefkowitz is from the last century 60's began torelated research, then the research content is adrenocorticotropic hormone.Got this important hormone receptors in the successful separation, and aftersuccessfully analyzed its mechanism of action of more than ten years, the research team he led the first cloned encoding this receptor gene. In the early 80's, the cloning of a gene is like looking for a needle in a haystack, andanother winner postdoctoral Lefkowitz recruit -- that is the Nobel prize -Kebierka do. Cloning of the gene would be the key they pushed the Nobelprize winner of the throne, as they soon discovered that the structure of thereceptor and before the discovery of light by stereological porphyrin somewhatsimilar

“这两种感受完全不同类型的刺激受体会不会是有联系的？”他们灵光一闪的念头使得G蛋白偶联受体家族被建立起来，因为他们知道肾上腺皮质激素受体与光受体结构类似，且都与G蛋白相互作用，当时人们所知道的类似的受体还有三十多个——这些受体拥有相似的，埋藏在细胞膜内的跨膜区域，但是暴露在细胞内与细胞外的部分千差万别。[2]

\related?\They flash idea makes the G protein coupled receptor family is established, because they know the similar glucocorticoid receptor and the light receptor structure, and interacts with G, the people know that at the time of the similar receptors have a 30 - these receptors havesimilar, buried in the transmembrane region within the cell membrane. But the exposed part vary widely in intracellular and extracellular. [2]

这个家族的建立大大推动了人类对细胞信号转导途径的认识。之后的二十多年里，随着生物学的发展日新月异，人们对这条途径的理解已经十分深刻，而且也被广泛应用。很多人类疾病与G蛋白偶联受体相关，因此它是制药行业重点研究的对象。据统计，在所有现代药物中，有40%以上是以G蛋白偶联受体作为靶点的。 [8] 其中著名的药物包括奥氮平、氯雷他定、雷尼替丁、替加色罗等等。

The establishment of the family greatly contributed to our understanding of the cell signal transduction pathway. After more than 20 years, with the development of biology with each passing day, the people understanding tothis approach has been very profound, but also widely used. Many humandiseases and G protein coupled receptor associated, so it is the research object of the focus of the pharmaceutical industry. According to statistics, in all modern medicine, there are more than 40% to the G protein coupled receptoras a target. [8] one well-known drugs including olanzapine, loratadine, Rene Titi, tegaserod etc..

科比尔卡2011年在此领域又取得了另一项重大突破：他和他的研究团队通过X射线晶体衍射的手段解出了β-肾上腺素受体被激素激活、向细胞发送信号时的结构——这是几十年来

肾上腺皮质激素受体研究的又一重要成果，一方面为为G蛋白偶联受体信号转导途径的作用机制提供了最直接的实验证据，一方面也为将来的研究提供了更多值得参考的细节。 Kebierka 2011 in this field and achieved another major breakthrough: he and his research team by X ray diffraction method solved the beta adrenergic receptor was structure hormone activated, sends a signal into the cell when -this is another important achievement of decades of adrenal cortical hormonereceptor studies, hand. To provide the most direct experimental evidence for the mechanism of G protein coupled receptor signal transduction pathway,offers a more details worth reference for future research.

G蛋白偶联受体（蓝色）、三聚体G蛋白（红色）与激素（黄色）结合时的晶体结构。[6]

一项前后进行了43年的杰出研究最终获得了诺贝尔奖，功夫不负有心人。科学，是值得奉献一生的事业。

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