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1、 蛋白质的研究历史与方法 第一节 蛋白质研究的历史回顾 蛋白质是一类重要的生物大分子， protein字源出自希腊文，是“最原初 的”，“第一重要的” 意思 19世纪30年代中期以前，认识其化学 元素组成情况及原子之间结合比例，即 确定经验性的分子式 1937年，A. W. k. Tiselius 建立了研究蛋白质 的移动界面电泳(electrophoresis )方法, 于1948年 获诺贝尔化学奖 1941年，A. J. P. Martin和R. L. M. Synge 建立了分配层析(partition chromatography) 技术，被授予1952年的诺贝尔化学奖 The Nob
2、el Prize in Chemistry 1948 for his research on electrophoresis and adsorption analysis, especially for his discoveries concerning the complex nature of the serum proteins Arne W. K. Tiselius Uppsala University Uppsala, Sweden 1902 - 1971 The Nobel Prize in Chemistry 1952 for their invention of parti
3、tion chromatography Archer J. P. MartinRichard L. M. Synge 1/2 of the prize 1/2 of the prize National Institute for Medical Research London, United Kingdom Rowett Research Institute Bucksburn (Scotland), United Kingdom 1910 - 20021914 - 1994 1953年，F. Sanger利用纸层析和纸 电泳技术第一次揭示出牛胰岛素的一级 结构，开创了以后数千种蛋白质序列分
4、 析的先声，被授予1958年诺贝尔化学奖 The Nobel Prize in Chemistry 1958 for his work on the structure of proteins, especially that of insulin Frederick Sanger University of Cambridge Cambridge, United Kingdom 1918 - The Nobel Prize in Chemistry 1980 for his fundamental studies of the biochemistry of nucleic acids, w
5、ith particular regard to recombinant-DNA for their contributions concerning the determination of base sequences in nucleic acids Paul Berg 1/2 of the prize Stanford University Stanford, CA, USA 1926 - Walter Gilbert Frederick Sanger 1/4 of the prize 1/4 of the prize Harvard University, Biological La
6、boratories Cambridge, MA, USA MRC Laboratory of Molecular Biology Cambridge, United Kingdom 1932 - 1918 - J. C. Kendrew (1958)及M. F. Perutz (1960) 利用X射线技术解析了肌红蛋白 (myoglobin)和血红蛋白(hemoglobin)的三 维结构，使人们第一次能够洞察生物大分 子的空间结构，共同赢得了1962年的诺贝 尔化学奖 The Nobel Prize in Chemistry 1962 for their studies of the str
7、uctures of globular proteins Max Ferdinand Perutz 1/2 of the prize MRC Laboratory of Molecular Biology Cambridge, United Kingdom 1914 - 2002 John Cowdery Kendrew 1/2 of the prize MRC Laboratory of Molecular Biology Cambridge, United Kingdom 1917 - 1997 20世纪70年代中后期，Gunter Blobel利用体外 蛋白质翻译系统发现动物细胞中很多分
8、泌蛋白的 跨膜方式，提出“信号假说”(signal hypothesis)， 获得了1998年的诺贝尔生理医学奖 20世纪50年代后期，E. W.Sutherland发现 细胞内cAMP的存在，1971年被授予诺贝尔生 理医学奖 70年代末80年代初， A. G. Gilman和M. Rodbell独立发现G蛋白的存在，因此二人在 1994年获得诺贝尔生理医学奖 “信号转导”(signal transduction) The Nobel Prize in Physiology or Medicine 1994 for their discovery of G-proteins and the
9、role of these proteins in signal transduction in cells Alfred G. GilmanMartin Rodbell 1941 - 1925 - 1998 University of Texas, Southwestern Medical Center Dallas, TX, USA National Institute of Environmental Health Sciences Research Triangle Park, NC, USA 60年代，P. Mitchell提出“化学渗透学说”， 获1978年获诺贝尔化学奖 70年代
10、，P. D. Boyer提出“结合改变机制”； 90年代，J. E. Walker测定ATP合酶的晶体结 构，他们共享了1997年的诺贝尔化学奖 揭示能量转化机制 The Nobel Prize in Physiology or Medicine 1993 for contributions to the developments of methods within DNA-based chemistry Michael Smith 1944 -1932 - 2000 La Jolla, CA, USA Kary B. Mullis University of British Columbia
11、 Vancouver, Canada for his invention of the polymerase chain reaction (PCR) method for his fundamental contributions to the establishment of oligonucleotide-based, site-directed mutagenesis and its development for protein studies Nature 1998; 391: 806-811. Potent and specific genetic interference by
12、 double- stranded RNA in Caenorhabditis elegans. What Roger Kornberg himself has now done is to describe how the genetic information is copied from DNA into what is called messenger-RNA Kornberg had described how genetic information is transferred from a mother cell to its daughters. The Nobel Prize
13、 in Physiology or Medicine 2007 for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells Mario R. Capecchi Sir Martin J. Evans Oliver Smithies USA United Kingdom USA University of Utah Salt Lake City, UT, USA; Howard Hughes Medical In
14、stitute b. 1937 (in Italy) Cardiff University Cardiff, United Kingdom b. 1941 University of North Carolina at Chapel Hill Chapel Hill, NC, USA b. 1925 (in United Kingdom) The Nobel Prize in Chemistry 2008 for the discovery and development of the green fluorescent protein, GFP Osamu Shimomura Martin
15、Chalfie Roger Y. Tsien 1/3 of the prize 1/3 of the prize 1/3 of the prize USA USA USA Marine Biological Laboratory (MBL) Woods Hole, MA, USA; Boston University Medical School Massachusetts, MA, USA b. 1928 (in Kyoto, Japan) Columbia University New York, NY, USA b. 1947 University of California San Diego, CA, USA; Howard Hughes Medical Institute b. 1952 The Nobel Prize in P
