● Chaperones do not convey additional information required for the folding of polypeptides into their correct three-dimensional conformations.
● The folded conformation of a protein is determined solely by its amino acid sequence. ● Rather, chaperones catalyze protein folding by assisting the self-assembly process. ●They appear to function by binding to and stabilizing unfolded or partially folded polypeptides that are intermediates along the pathway leading to the final correctly folded state.
, GroEL GroEL, GroES of E.coli in protein folding
Sequential actions of Hsp70 and Hsp60 chaperones
Action of chaperones in signaling
Action of chaperones during protein transport
◆It is important to note that :
: ◆该概念有以下特点 该概念有以下特点:
,都称为分子伴 ●凡具有“介导”功能的蛋白 功能的蛋白, ; 侣,可以是完全不同的蛋白质 可以是完全不同的蛋白质; , 故用“ 介导 ” 二字 ,伸 ● 作用机理尚不清楚 作用机理尚不清楚, 二字, 缩性较大； ●分子伴侣一定不是最终结构的组成部分 , ; 但不一定是一个分离的实体 但不一定是一个分离的实体; , 包括 : 帮助新生肽的 ● 装配的涵意比较广 装配的涵意比较广, 包括: ,越膜定位 , 亚基组装等。 折叠 折叠, 越膜定位,
�核孔
◆由内外两层膜的局部融合而成 80-120nm 。 ◆核孔的直径为 核孔的直径为80-120nm 80-120nm。 3000◆ 一个典型的哺乳动物的核膜上有 一个典型的哺乳动物的核膜上有30004000 个核孔 ,相当于每平方微米的核膜上 4000个核孔 个核孔, 个。 有10-60 10-60个。 ◆合成功能旺盛的细胞 ,核孔的数量较多。 合成功能旺盛的细胞,
Molecular Chaperones
◆应激反应 ●Molecular chaperones were initially identified as heatshock proteins, a group of proteins expressed in cells that have been subjected to elevated temperatures or other forms of environmental stress. ●The heat-shock proteins (abbreviated Hsp ), which are Hsp), highly conserved in both prokaryotic and eukaryotic cells, are thought to stabilize and facilitate the refolding of proteins that have been partially denatured as a result of exposure to elevated temperature. ●However, many members of the heat-shock protein family are expressed and have essential cellular functions under normal growth conditions. ●These proteins serve as molecular chaperones, which are needed for polypeptide folding and transport under normal conditions as well as in cells subjected to environmental stress.
分 子 伴 侣 的 基 本 功 能
◆ 分 子 内 伴 侣 (intromolecular chaperones)
◆分子伴侣的分布 ,从动物到植物 ●从细菌到人 从细菌到人, ●细胞质、线粒体、叶绿体和微体
同特点 �分子伴侣结构上的共 分子伴侣结构上的共同特点
◆家族成员具有高度保守性 ◆家族成员结构上具有相似性 , 在刺激条件下会 ◆ 大部分在体内为组成型表达 大部分在体内为组成型表达, 被进一步诱导。
Model of the nuclear pore complex
Nuclear Pore Complexes
Model of the nuclear pore complex
�核孔运输特点 ◆被动运输 ◆主动运输 ●信号引导 ●双向性
核孔的运输作用
核孔的被动运输
核孔的双向运输
?
核孔运输的信号引导
的输出 mRNA mRNA的输出
核内 蛋白质的输出 核内蛋白质的输出
的输出 snRNA snRNA的输出
11.3
分
子
伴
侣 �分子伴侣的概念及其特点
年Ellis 等人提出 : ◆1991 1991年 Ellis等人提出 等人提出: ●由不相关类的蛋白质组成的一个家系 ●它们介导其它蛋白质的正确装配 。 ●但自己不成为最后功能结构中的组分 但自己不成为最后功能结构中的组分。
细胞胞胞 胞核核核 核 细细细
11.1 Nuclear Envelope
11.1.1 Structure of the Nuclear Envelope
�一般结构 ◆Outer nuclear membrane ◆Inner nuclear membrane ◆Perinuclear space 两层核膜之间的空隙, 宽15-30nm, 其中充满无定形物质 ◆核纤层(lamina)
DNA 三种不同构型的 三种不同构型的DNA
结构稳定遗传的功能序列 �DNA DNA结构稳定遗传的功能序列 ◆ARS (autonomous replicating sequence) centromeric sequence) ◆CEN ( (centromeric The centromere is a specialized region of the chromosome that plays a critical role in ensuring the correct distribution of duplicated chromosomes to daughter cells during mitosis ◆ TEL(telomeric sequence) The sequences at the ends of eukaryotic chromosomes, called telomeres, play critical roles in chromosome replication and maintenance.
构型中 ,沟的特征在遗传信息表达过 三种 DNA DNA构型中 构型中, ,调控蛋白都是通过其分子上 程中起关键作用 程中起关键作用, 氨基酸侧链与沟中碱基对两侧潜在的氢原子 (=NH) 或受体 (O 和 N) 形成氢键而识别 DNA 供体 供体(=NH) (=NH)或受体 或受体(O (O和 N)形成氢键而识别 形成氢键而识别DNA 另外 , Z 型 DNA 同细胞癌变有一 遗传信息的。 遗传信息的。另外 另外, Z型 DNA同细胞癌变有一 定的关系。
CHAPTER 11
Cell Nucleus and Chromosome
OUTLINE
1.NUCLEAR ENVELOPE 2.TRANSPORT THROUGH NUCLEAR PORE COMPLEXE 3.MOLECULAR CHAPERONE 4.CHROMATIN 5.CHROMOSOME 6.NUCLEOLUS
11.3.1 分子伴侣的发现及种类 (chaperones)
◆The term “chaperone" was first used by Ron Laskey and his colleagues to describe a protein ) that is required for the assembly (nucleoplasmin nucleoplasmin) of nucleosomes from histones and DNA. ◆Nucleoplasmin binds to histones and mediates their assembly into nucleosomes , but nucleosomes, nucleoplasmin itself is not incorporated into the final nucleosome structure. ◆Chaperones thus act as catalysts that facilitate assembly without being part of the assembled complex.
�如何理解细胞核
◆遗传学 ◆生物化学 ◆细胞生物学 ●结构 ●功能 , 保持细 ▲ 通过遗传物质的复制和细胞分裂 通过遗传物质的复制和细胞分裂, (遗传 ); 胞世代间的连续性 胞世代间的连续性( 遗传); , 控制细胞的代谢 ▲ 通过基因的选择性表达 通过基因的选择性表达, ,以适应外界环境。 活动 活动,