《细胞膜和细胞表面》PPT课件.ppt

细胞膜与细胞表面 plasma membrane and cell surface,膜脂 Lipid Composition and Structural Organization,生物膜的结构基础，脂质双分子层 Biomembranes: Lipid Composition and Structural Organization,膜脂生物膜的基本组成成分 Three Classes of Lipids Are Found in Biomembranes,膜脂可分为三大类，磷脂（磷脂甘油），鞘脂和胆固醇 A typical biomembrane is assembled from phosphoglycerides,sphingolipids, and steroids. All three classes of lipids are amphipathic molecules having a polar (hydrophilic) head group and hydrophobic tail.,磷脂甘油 3-磷酸甘油的衍生物 the most abundant class of lipids in most membranes, are derivatives of glycerol 3-phosphate .,磷脂具有2个脂酰基构成的疏水性尾部和与磷酸相连的亲水性头部 A typical phosphoglyceride molecule consists of a hydrophobic tail composed of two fatty acyl chains esterified to the two hydroxyl groups in glycerol phosphate and a polar head group attached to the phosphate group.,Phosphatidylethanolamine 磷脂酰乙醇胺 Phosphatidylcholine 磷脂酰胆碱 Phosphatidylserine 磷脂酰丝氨酸 Phosphatidylinositol 磷脂酰肌醇,红色部分为鞘氨醇，具有一个长的碳氢链，一个氨基与脂肪酸链相连，一个羟基和磷酸相连 All of these compounds are derived from sphingosine, an amino alcohol with a long hydrocarbon chain, and contain a long-chain fatty acid attached to the sphingosine amino group.,sphingomyelins,鞘磷脂,Glucosylcerebroside，葡萄糖神经酰胺，是一种糖脂，糖脂在神经组织最多 Glycolipids constitute 210 percent of the total lipid in plasma membranes; they are most abundant in nervous tissue.,胆固醇，有4个环，一个羟基（亲水） 前面两种膜脂可以单独或混合形成脂双层，胆固醇则不能形成脂双层。 Cholesterol is especially abundant in the plasma membranes of mammalian cells but is absent from most prokaryotic cells. As much as 3050 percent of the lipids in plant plasma membranes consist of certain steroids unique to plants.,膜脂在细胞质侧和外侧的分布不一样 Membrane Lipids Are Usually Distributed Unequally in the Exoplasmic and Cytosolic Leaflets,在红细胞，鞘脂和磷脂胆碱，分布细胞外侧，磷脂乙醇胺，磷脂丝氨酸，磷脂肌醇，分布在细胞内侧 in plasma membranes from human erythrocytes, almost all the sphingomyelin and phosphatidylcholine, both of which form less fluid bilayers, are found in the exoplasmic leaflet. In contrast, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol, which form more fluid bilayers, are preferentially located in the cytosolic leaflet.,脂双层结构的形成,the polar head groups in all phospholipids can pack together into the characteristic bilayer structure. Sphingomyelins are similar in shape to phosphoglycerides and can form mixed bilayers with them. Cholesterol and other steroids are too hydrophobic to form a bilayer structure unless they are mixed with phospholipids.,膜的侧面流动性和脂肪酸链长度，饱和或不饱和脂肪酸，及温度有关。 膜脂的流动性限制了膜蛋白的流动性,The ability of lipids to diffuse laterally in a bilayer indicates that it can act as a fluid. The degree of bilayer fluidity depends on the lipid composition Long, saturated fatty acyl chains have the greatest tendency to aggregate, packing tightly together into a gel-like state.,膜蛋白荧光标记脱色恢复实验,膜脂的运动方式,沿膜平面侧向运动 围绕轴心的自旋 分子尾部的摆动 双层分子间的翻转 依赖于翻转酶flipase,脂筏Lipid raft,鞘脂和胆固醇形成，厚度和构成均和周围不同，脂筏可以集中某些蛋白。 The first hint that lipids may be organized within the leaflets was the discovery that the residues remaining after the extraction of plasma membranes with detergents contain two lipids: cholesterol and sphingomyelin. Because these two lipids are found in more ordered, less fluid bilayers, researchers hypothesized that they form microdomains, termed lipid rafts, surrounded by other more fluid phospholipids that are easily extracted by detergents.,Lipid droplets are surrounded by a phospholipid monolayer,脂质体（liposome）,脂质体是根据磷脂分子可在水相中形成稳定的脂双层膜的趋势而制备的人工膜。,脂质体的类型和应用,(a)水溶液中的磷脂分子团； (b)球形脂质体； (c)平面脂质体膜； (d）用于疾病治疗的脂质体的示意图,脂质体的应用 研究膜脂与膜蛋白及其生物学性质； 脂质体中裹入DNA可用于基因转移； 在临床治疗中,脂质体作为药物或酶等载体,膜蛋白 Biomembranes: Protein Components and Basic Functions,膜蛋白分内在蛋白，锚定蛋白，外周蛋白 Proteins Interact with Membranes in Three Different Ways Integral membrane proteins, Lipid-anchored membrane proteins Peripheral membrane proteins,蛋白穿膜部分的主要二级结构是螺旋 Membrane-Embedded Helices Are the Primary Secondary Structures in Most Transmembrane Proteins,血型糖蛋白，跨膜螺旋由20-25个疏水性氨基酸构成 Structure of glycophorin A, a typical singlepass transmembrane protein. Typically, a membrane-embedded helix is composed of 2025 hydrophobic (uncharged) amino acids. The predicted length of such a helix (3.75 nm) is just sufficient to span the hydrocarbon core of a phospholipid bilayer. The hydrophobic side chains protrude outward from the helix and form van der Waals interactions with the fatty acyl chains in the bilayer.,七次跨膜螺旋在很多跨膜蛋白中存在，如G蛋白偶联受体，细菌中的细菌视紫质。 A large and important family of integral proteins is defined by the presence of seven membrane-spanning helices. Among them are the G proteincoupled receptors. The structure of bacteriorhodopsin, a protein found in the membrane of certain photosynthetic bacteria, illustrates the general structure of all these proteins,细菌视紫质结构模型,离子通道也是多次跨膜蛋白家族,钾离子通道由四聚体构成，每个亚单位有一对跨膜螺旋，螺旋的方向改变调节离子的流动。 Ion channels compose a second large and important family of multipass transmembrane proteins. As revealed by the crystal structure of a resting K+ channel, ion channels are typically tetrameric proteins. Each of the four subunits has a pair of membrane-spanning helices that bundle with helices of other subunits, forming a central channel,Multiple Strands in Porins Form embrane-Spanning “Barrels,革兰氏阴性细菌外膜中孔道蛋白，可以小分子亲水物质进出，防止对细菌有害的进入。 The porins are a class of transmembrane proteins whose structure differs radically from that of other integral proteins. Several types of porin are found in the outer membrane of gram-negative bacteria such as E. coli and in the outer membranes of mitochondria and chloroplasts. The outer membrane protects an intestinal bacterium from harmful agents (e.g., antibiotics, bile salts, and proteases) but permits the uptake and disposal of small hydrophilic molecules including nutrients and waste products. The porins in the outer membrane of an E. coli cell provide channels for the passage of disaccharides and other small molecules as well as phosphate.,去垢剂detergent,去垢剂是一端亲水、另一端疏水的两性小分子,是分离与研究膜蛋白的常用试剂。 离子型去垢剂(SDS)和非离子型去垢剂（Triton X-100） SDS: CH3-(CH2)11-OSO3-Na+ ,细胞膜和细胞骨架相互影响 Interactions with the Cytoskeleton Impede the Mobility of Integral Membrane Proteins,与蛋白在人工脂质体上的表现不同，在活细胞里，蛋白的移动速率要低的多1/10-30 。 However, the diffusion rate of a protein in the plasma membrane of intact cells is generally 1030 times lower than that of the same protein embedded in synthetic spherical bilayer structures (liposomes). These findings suggest that the mobility of integral proteins in the plasma membrane of living cells is restricted by interactions with the rigid submembrane cytoskeleton.,生物膜一些概念,单位膜 流动镶嵌模型,细胞连接 CellCell and CellMatrix Adhesion,INTEGRATING CELLS INTO TISSUES,细胞通过细胞粘连分子相互连接 Cells in tissues can adhere directly to one another (cellcell adhesion) through specialized integral membrane proteins called cell-adhesion molecules (CAMs) that often cluster into specialized cell junctions,cell-adhesion molecules (CAMs),细胞黏连分子分成钙黏素，免疫球蛋白超家族，整合素，选择素。 其他参加细胞粘连的膜蛋白 A large number of CAMs fall into four major families: the cadherins, immunoglobulin (Ig) superfamily, integrins, and selectins. Some other membrane proteins, whose structures do not belong to any of the major classes of CAMs, also participate in cellcell adhesion in various tissues.,相同粘连分子的连接称为同亲性homophilic binding，不同粘连分子连接称为异亲性heterophilic binding 细胞粘连可以是牢固的，如上皮细胞间的连接；也可以是微弱的，短暂的，如免疫细胞穿越血管内皮。 Cellcell adhesions can be tight and long lasting or relatively weak and transient. The associations between nerve cells in the spinal cord or the metabolic cells in the liver exhibit tight adhesion. In contrast, immune-system cells in the blood can exhibit only weak, short-lasting interactions, allowing them to roll along and pass through a blood vessel wall on their way to fight an infection within a tissue.,细胞粘连分子先形成二聚体或寡聚体，这种作用是细胞内的，然后在不同细胞间粘连分子相互连接，这种作用是细胞间的，后者能促进细胞内的聚合。 First, CAMs on one cell associate laterally through their extracellular domains or cytosolic domains or both into homodimers or higher-order oligomers in the plane of the cells plasma membrane; these interactions are called intracellular, lateral, or cis interactions. Second, CAM oligomers on one cell bind to the same or different CAMs on an adjacent cell; these interactions are called intercellular or trans interactions. Trans interactions sometimes induce additional cis interactions and, as a consequence, yet even more trans interactions.,上皮细胞间的连接和粘连分子 Sheetlike Epithelial Tissues: Junctions and Adhesion Molecules,上皮细胞可分成游离面，基底面和侧面 the distinct surfaces of a polarized epithelial cell are called the apical (top), basal (base or bottom), and lateral (side) surfaces,3类连接，锚定，紧密，缝隙,锚定连接对应桥粒和中间链接，起绑定细胞作用，紧密连接封闭细胞间缝隙。缝隙连接在相邻细胞间扩散亲水性小分子。 Three major classes of animal cell junctions are prominent Anchoring junctions and tight junctions perform the key task of holding cells together into tissues. Tight junctions also control the flow of solutes between the cells forming an epithelial sheet. Gap junctions permit the rapid diffusion of small, water-soluble molecules between the cytoplasm of adjacent cells.,钙粘素（Cadherins）,属同亲性依赖Ca2+的细胞粘连糖蛋白，介导依赖Ca2+的细胞粘着和从ECM到细胞质传递信号。对胚胎发育中的细胞识别、迁移和组织分化以及成体组织器官构成具有主要作用。 E- Cadherins(epithelial), N- Cadherins(neural) ，,钙黏素介导细胞间钙依赖同亲性粘着（中间连接，桥粒） Ca2+-Dependent Homophilic CellCell Adhesion in Adherens Junctions and Desmosomes Is Mediated by Cadherins,E-钙黏素介导的中间连接。钙黏素的细胞部分通过接头蛋白和肌动蛋白纤维相连。,桥粒钙黏素， Desmosomal Cadherins,细胞部分的接头蛋白形成斑块状，通过其与中间纤维相连 contain two specialized cadherin proteins, desmoglein and desmocollin, whose cytosolic domains are distinct from those in the classical cadherins. The cytosolic domains of desmosomal cadherins interact with plakoglobin and the plakophilins. These adapter proteins, which form the thick cytoplasmic plaques characteristic of desmosomes, in turn interact with intermediate filaments.,紧密连接封闭细胞间缝隙，限制膜流动 Tight Junctions Seal Off Body Cavities and Restrict Diffusion of Membrane Components,紧密连接形成屏障，将细胞两侧液体分开 For polarized epithelial cells to carry out their functions as barriers and mediators of selective transport, extracellular fluids surrounding their apical and basolateral membranes must be kept separate.,紧密连接中的2种主要蛋白occludin and claudin. The two principal integral-membrane proteins found in tight junctions are occludin and claudin.,另外一种分子JAMs，属于免疫球蛋白超家族 Recently, a group of junction adhesion molecules (JAMs) have been found to contribute to homophilic adhesion and other funct