错误折叠与蛋白质构象病misfoldingandproteinconformational.PPT

DNA RNA Proein 为什么要开展蛋白质折叠的研究? 研究的源动力 蛋白质研究先驱 １９１２年到美国麻省理工学院。因愤于我国海军落后，初学造船工程。因受赫胥黎“生命的物理基础”一文的影响，２年后改习化学。１９１６年毕业，获理学学士学位，留校任化学系助教。１９１７年进哈佛大学医学院生物系，成为美国著名生物化学家 Folin教授的研究生，进行血液化学研究。1924年起用各种方法使蛋白质变性，1931年得出如下理论：蛋白质的变性是由于蛋白质分子由折叠而变为舒展。 Some denatured proteins can be renatured Probability that correct folding would occur in ribonuclease Mechanisms to explain re-folding Factors driving protein folding Energy surfaces to visualize protein folding pathways Changes of fluorescence emission spectra of Tg denatured in various concentrations of GuHCl ANS binding characteristics of Tg in various GuHCl concentrations 蛋白质功能区 肌酸激酶活性部位荧光探针暴露的速度常数 酶活性部位的柔性学说 邹承鲁 药物研究 开阔思路 记忆合金棒矫正脊柱侧凸 卢世璧 (院士) 分子伴侣molecular chaperones Misfolding Protein Conformational Disorders Prion Protein Gene (PRNP) The Nobel Prize in Physiology or Medicine 1976for their discoveries concerning new mechanisms for the origin and dissemination of infectious diseases Stanley B. PrusinerThe Nobel Prize in Physiology or Medicine 1997for his discovery of Prions - a new biological principle of infection References Roger H.Pain， Mechanisms of Protein Folding Bengt N?lting， Proein Folding Kinetics –Biophysical Methods Leninger, Principles of Biochemistry,Worth Publishing, Mathews and Van Holde, Biochemistry, Benjamin Cummings 抗氧化剂对A?1-40结构的影响 庾照学等,中国病理生理杂志,2000,16 FT - IR spectra of A?1 - 40 in PBS(pH7. 4) for 30min FT - IR spectra of A?1 - 40 in PBS(pH7. 4) for 7 days FT - IR spectra of A?1 - 40 in PBS(pH7. 4) for 7 days FT- IR spectra of A?1 - 40 in PBS(pH7. 4) with TA9901 for 7 days (percent ratio : A?1 – 40 :TA9901 = 1∶1) 衰 减 全 反 射 红 外 光 谱 ?研究人乳腺癌组织 0.09 0.37 0.56 0.23 0.43 malignant 0.17 0.49 0.64 0.65 0.98 benign A1682/A1652 A1662/A1652 A1645/A1652 A1625/A1652 A1635/A1652 HSP 肿瘤疫苗 新生肽链的折叠 疯牛病带给生命科学界的思考 Mad cow TSE Alzheimer’s D. Amyloid ? Protein Tau protein Familial visceral Amyloidosis Lysozyme …. Parkinso