第二蛋白质的结构与功能精要.ppt

八聚体组蛋白核心2(H2A,H2B,H3,H4) 蛋白质空间结构的总结 一级结构蛋白质的空间结构基础，蛋白质趋向形成一种能量最低，结构最稳定的三级结构，这是蛋白质能折叠的动力； 细胞内高稠密介质，以及狭窄空间使得伸展的和部分折叠的蛋白质在高浓度时倾向于聚集；无法自我迅速完成正确折叠； “辅助性组装学说”（assisted assembling）：新生肽链折叠并组装成有功能的蛋白质并非都能自发完成，在相当多的情况下是需要其他蛋白质帮助的，这类帮助蛋白包括分子伴侣（molecular chaperones）和折叠酶（folding enzymes, foldases）。 蛋白质的折叠问题 两大类蛋白质参与蛋白质折叠： 折叠酶：蛋白质二硫键异构酶（protein disulfide isomerase, PDI）:加速蛋白质折叠过程中形成正确配对二硫键；肽基脯氨酰顺反异构酶（peptidyl prolyl cis/trans isomerase,PPI） 分子伴侣（molecular chaperone）:为蛋白质折叠提供一个有利的折叠环境，与未折叠肽段的疏水部分可逆结合，防止聚集和错误折叠，诱导正确折叠。如热休克蛋白（heat shock protein）等 1987,Lasky: molecular chaperone 分子伴侣主要的分类： 伴侣素家族（chaperonin,Cpn） 应激蛋白70家族（stress-70 family）/热休克蛋白70家族（Hsp 70 family） 应激蛋白90家族（stress-90 family）/热休克蛋白90家族（Hsp 90 family） 伴侣素家族（chaperonin, Cpn） The structure and function of the hsp60 family of molecular chaperones. (A) The catalysis of protein refolding. As indicated, a misfolded protein is initially captured by hydrophobic interactions along one rim of the barrel. The subsequent binding of ATP plus a protein cap increases the diameter of the barrel rim, which may transiently stretch (partly unfold) the client protein. This also confines the protein in an enclosed space, where it has a new opportunity to fold. After about 15 seconds, ATP hydrolysis ejects the protein, whether folded or not, and the cycle repeats. This type of molecular chaperone is also known as a chaperonin; it is designated as hsp60 in mitochondria, TCP-1 in the cytosol of vertebrate cells, and GroEL in bacteria. As indicated, only half of the symmetrical barrel operates on a client protein at any one time. (B) The structure of GroEL bound to its GroES cap, as determined by x-ray crystallography. On the left is shown the outside of the barrel-like structure and on the right a cross section through its center. The hsp70 family of molecular chaperones. These proteins act early, recognizing a small stretch of hydrophobic amino acids on a proteins surface. Aided by a set of smaller hsp40 proteins, an hsp70 monomer binds t