细胞膜和细胞表面ppt课件

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1、细胞膜与细胞外表细胞膜与细胞外表plasma membrane and cell surface膜脂膜脂 Lipid Composition and Structural Organizationn生物膜的构造根底，生物膜的构造根底，脂质双分子层脂质双分子层nBiomembranes:Lipid Composition and Structural Organization膜脂生物膜的根本组成成分Three Classes of Lipids Are Foundin Biomembranesn膜脂可分为三大类，磷脂磷脂甘油，鞘脂和胆固醇nA typical biomembrane is ass

2、embled 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 inmost 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

3、水性头部A typical phosphoglyceride molecule consistsof 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Pho

4、sphatidylinositol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Gl

5、ycolipids constitute 210 percent of the total lipid in plasma membranes;they are most abundant in nervous tissue.n胆固醇，有4个环，一个羟基亲水n前面两种膜脂可以单独或混合构成脂双层，胆固醇那么不能构成脂双层。nCholesterol is especially abundant in the plasma membranes of mammalian cells but is absent from most prokaryotic cells.As much as 3050 p

6、ercent 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 Leafletsn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nin plasma membranes from human erythrocy

7、tes,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.脂双层构

8、造的构成nthe 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 mi

9、xed 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nThe 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 compositionnLong,saturated fatty acyl chains have the greatest tendency to aggregate

10、,packing tightly together into a gel-like state.膜蛋白荧光标志脱色恢复实验膜脂的运动方式n沿膜平面侧向运动n围绕轴心的自旋n分子尾部的摆动n双层分子间的翻转n依赖于翻转酶flipase脂筏Lipid raftn鞘脂和胆固醇构成，厚度和构成均和周围不同，脂筏可以集中某些蛋白。nThe first hint that lipids may be organized within the leaflets was the discovery that the residues remaining after the extraction of plas

11、ma 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 deter

12、gents.Lipid droplets are surrounded by a phospholipid monolayer脂质体liposomen脂质体是根据磷脂分子可在水相中构成稳定的脂双层膜的趋势而制备的人工膜。脂质体的类型和运用(a)(a)水溶液中的磷脂分子团；水溶液中的磷脂分子团；(b)(b)球形脂质体；球形脂质体；(c)(c)平面脂质体膜；平面脂质体膜；(d(d用于疾病治疗的脂质体的表示图用于疾病治疗的脂质体的表示图脂质体的运用研讨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膜蛋白Biomembranes:Protei

13、nComponents and Basic Functionsn膜蛋白分内在蛋白，锚定蛋白，外周蛋白nProteins Interact with Membranes in Three Different WaysnIntegral membrane proteins,nLipid-anchored membrane proteinsnPeripheral membrane proteins蛋白穿膜部分的主要二级构造是蛋白穿膜部分的主要二级构造是螺旋螺旋Membrane-Embedded Helices Are the Primary Secondary Structures in Most

14、Transmembrane Proteinsn血型糖蛋白，跨膜螺旋由20-25个疏水性氨基酸构成nStructure 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 cor

15、e 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.n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。nA large and important family of integral proteins is defined by the presence of seven membrane-s

16、panning 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细菌视紫质构造模型离子通道也是多次跨膜蛋白家族n钾离子通道由四聚体构成，每个亚单位有一对跨膜螺旋，螺旋的方向改动调理离子的流动。nIon channels com

17、pose 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

18、 a central channelMultiple Strands in Porins Form embrane-Spanning“Barrelsn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。nThe 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-neg

19、ative 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

20、 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detergentn去垢剂是一端亲水、另一端疏水的两性小分子,是分别与研讨膜蛋白的常用试剂。n离子型去垢剂(SDS)和非离子型去垢剂Triton X-100nSDS:CH3-(CH2)11-OSO3-Na+细胞膜和细胞骨架相互影响细胞膜和细胞骨架相互影响Interactions

21、 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，蛋白的挪动速率要低的多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 structur

22、es(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n单位膜n流动镶嵌模型细胞衔接CellCell and CellMatrix Adhesion,INTEGRATING CELLS INTO TISSUESn细胞经过细胞粘连分子相互衔接nCells in tissu

23、es can adhere directly to one another(cellcell adhesion)through specialized integral membrane proteins called cell-adhesion molecules(CAMs)that often cluster into specialized cell junctionscell-adhesion molecules(CAMs)n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。n其他参与细胞粘连的膜蛋白nA large number of CAMs fall into four

24、major families:the cadherins,immunoglobulin(Ig)superfamily,integrins,and selectins.nSome other membrane proteins,whose structures do not belong to any of the major classes of CAMs,also participate in cellcell adhesion in various tissues.n一样粘连分子的衔接称为同亲性homophilic binding，不同粘连分子衔接称为异亲性heterophilic bin

25、dingn细胞粘连可以是结实的，如上皮细胞间的衔接；也可以是微弱的，短暂的，如免疫细胞穿越血管内皮。nCellcell 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 exh

26、ibit 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.n细胞粘连分子先构成二聚体或寡聚体，这种作用是细胞内的，然后在不同细胞间粘连分子相互衔接，这种作用是细胞间的，后者能促进细胞内的聚合。nFirst,CAMs on one cell associate laterally through their extracellular dom

27、ains 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

28、 called intercellular or trans interactions.Trans interactions sometimes induce additional cis interactions and,as a consequence,yet even more trans interactions.上皮细胞间的衔接和粘连分子上皮细胞间的衔接和粘连分子Sheetlike Epithelial Tissues:Junctions and Adhesion Moleculesn上皮细胞可分成游离面，基底面和侧面nthe distinct surfaces of a polar

29、ized epithelial cell are called the apical(top),basal(base or bottom),and lateral(side)surfaces3类衔接，锚定，严密，缝隙n锚定衔接对应桥粒和中间链接，起绑定细胞作用，严密衔接封锁细胞间缝隙。缝隙衔接在相邻细胞间分散亲水性小分子。nThree major classes of animal cell junctions are prominent nAnchoring junctions and tight junctions perform the key task of holding cells

30、 together into tissues.Tight junctions also control the flow of solutes between the cells forming an epithelial sheet.nGap junctions permit the rapid diffusion of small,water-soluble molecules between the cytoplasm of adjacent cells.钙粘素Cadherinsn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到细胞质传送信号。对胚胎发育中的细

31、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。nE-Cadherins(epithelial),nN-Cadherins(neural)，钙黏素介导细胞间钙依赖同亲性粘着中间衔接，桥粒钙黏素介导细胞间钙依赖同亲性粘着中间衔接，桥粒Ca2+-Dependent Homophilic CellCell Adhesionin Adherens Junctions and DesmosomesIs Mediated by CadherinsE-钙黏素介导的中间衔接。钙黏素的细胞部分经过接头蛋白和肌动蛋白纤维相连。桥粒钙黏素，Desmosomal Cadherins n细胞部分的接头蛋白构成斑

32、块状，经过其与中间纤维相连ncontain 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 cytop

33、lasmic plaques characteristic of desmosomes,in turn interact with intermediate filaments.严密衔接封锁细胞间缝隙，限制膜流动严密衔接封锁细胞间缝隙，限制膜流动Tight Junctions Seal Off Body Cavitiesand Restrict Diffusion of Membrane Componentsn严密衔接构成屏障，将细胞两侧液体分开nFor polarized epithelial cells to carry out their functions as barriers an

34、d mediators of selective transport,extracellular fluids surrounding their apical and basolateral membranes must be kept separate.严密衔接中的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 ju

35、nction adhesion molecules(JAMs)have been found to contribute to homophilic adhesion and other functions of tight junctions.细胞间的通路，缝隙衔接Passageways from cell to cell:gap junctionsn由六个由六个connexin构构成衔接子，成衔接子，中间有。中间有。1.5nm小孔。小孔。,相邻膜相邻膜衔接子对接构成跨膜衔接子对接构成跨膜通道。通道。nGap Junctions Composed of Connexins Allow Sma

36、ll Molecules to Pass Between Adjacent Cells选择素，在血液中介导细胞间粘着selectin mediate transient cell-cell adhesions in the bloodstreamn属异亲性依赖于Ca2+的能与特异糖基识别并相结合的糖蛋白，其胞外部分具有凝集素样构造域(lectin-like domain)。主要参与白细胞与血管淋巴管内皮细胞之间的识别与粘着。nSelecins are cell-surface carbohydrate-bingding proteins that mediate a variety of tr

37、ansient,cell-cell adhesins interactions in the bloodstream.n白细胞外表有L-选择素，血小板和炎症激活内皮细胞表达P-选择素，激活内皮细胞表达-E选择素。nThere are at least three types:L-selectin on white blood cells,P-selectin on blood platelets and on endothelial cells that have been locally activated by an inflammatory response,and E-selectin

38、 on activated endothelial cells.免疫球蛋白超家族的CAM(Ig-Superfamily，IgSF)n分子构造中具有与免疫球蛋白类似的构造域的CAM超家族。介导同亲性细胞粘着或介导异亲性细胞粘着,但其粘着作用不依赖Ca2+，其中N-CAMs 在神经组织细胞间的粘着中起主要作用。整合素Many CellMatrix and Some CellCellInteractions Are Mediated by Integrinsn由和两个亚基构成的异源二聚体糖蛋白。可与不同的配基结合，从而介导细胞与基质、细胞与细胞之间的粘着。问题n如何了解细胞膜流动镶嵌模型n膜脂的构成与膜的不对称性n细胞的严密衔接，中间衔接，桥粒，缝隙衔接与衔接分子关系。n从白细胞出血管，了解细胞粘连分子在其中的作用。