细胞膜的结构及探索历程课件.ppt

1、细胞质膜Overton(1890s):Lipid nature of PM;J.D.Robertson(1959):The TEM showing:the trilaminar appearance of PM;Unit membrane model;S.J.Singer and G.Nicolson(1972):fluid-mosaic model;K.Simons et al(1997):lipid rafts model;Singer and Nicolsons Model of membrane structure:The fluid-mosaic model is the“centr

2、al dogma”of membrane biology.The Fluid Mosaic Model,proposed in 1972 by Singer and Nicolson,had two key features,both implied in its name.Figure.The parts of a phospholipid molecule.Phosphatidylcholine（PC,磷脂酰胆碱）,represented schematically(A),in formula(B),as a space-filling model(C),and as a symbol(D

3、).The kink due to the cis-double bond（顺双键）is exaggerated in these drawings for emphasis.Figure.A lipid micelle（微囊）（微囊）and a lipid bilayer seen in cross-section（横断面）（横断面）.Lipid molecules form such structures spontaneously in water.The shape of the lipid molecule determines which of these structures i

4、s formed.Wedge-shaped lipid molecules(above)form micelles,whereas cylinder-shaped phospholipid molecules(below)form bilayers.Figure.Liposomes（脂质体）（脂质体）(A)An electron micrograph of unfixed,unstained phospholipid vesicles(liposomes)in water.The bilayer structure of the vesicles is readily apparent.(B)

5、A drawing of a small spherical liposome seen in cross-section.Liposomes are commonly used as model membranes in experimental studies.Figure.Six ways in which membrane proteins associate with the lipid bilayer.Most trans-membrane proteins are thought to extend across the bilayer as a single a helix(1

6、)or as multiple a helices(2);some of these“single-pass”and“multipass”proteins have a covalently attached fatty acid chain inserted in the cytoplasmic monolayer(1).Other membrane proteins are attached to the bilayer solely by a covalently attached lipid-either a fatty acid chain or prenyl group-in th

7、e cytoplasmic monolayer(3)or,less often,via an oligosaccharide,to a minor phospholipid,phosphatidylinositol(磷脂酰肌醇),in the noncytoplasmic monolayer(4).Finally,many proteins are attached to the membrane only by noncovalent interactions with other membrane proteins(5)and(6).Membrane proteinsFigure.A ty

8、pical single-pass transmembrane protein.Note that the polypeptide chain traverses the lipid bilayer as a right-handed a helix and that the oligosaccharide chains and disulfide bonds are all on the noncytosolic surface of the membrane.Disulfide bonds do not form between the sulfhydryl groups in the c

9、ytoplasmic domain of the protein because the reducing environment in the cytosol maintains these groups in their reduced(-SH)form.(3)Figure.The covalent attachment of either of two types of lipid groups can help localize a water-soluble protein to a membrane after its synthesis in the cytosol.(A)A f

10、atty acid chain(either myristic or palmitic acid)is attached via an amide linkage to an amino-terminal glycine.(B)A prenyl group(either farnesyl or a longer geranylgeranyl group-both related to cholesterol)is attached via a thioether linkage to a cysteine residue that is four residues from the carbo

11、xyl terminus.Following this prenylation,the terminal three amino acids are cleaved off and the new carboxyl terminus is methylated before insertion into the membrane.The structures of two lipid anchors are shown underneath:(C)a myristyl anchor(a 14-carbon saturated fatty acid chain),and(D)a farnesyl

12、 anchor(a 15-carbon unsaturated hydrocarbon chain).酰胺键酰胺键硫醚键硫醚键Figure.Solubilizing membrane proteins with a mild detergent.The detergent disrupts the lipid bilayer and brings the proteins into solution as protein-lipid-detergent complexes.The phospholipids in the membrane are also solubilized by the

13、 detergent.The use of mild detergents for solubilizing,purifying,and reconstituting functional membrane protein systems.In this example functional Na+-K+ATPase molecules are purified and incorporated into phospholipid vesicles.The Na+-K+ATPase is an ion pump that is present in the plasma membrane of

14、 most animal cells;it uses the energy of ATP hydrolysis to pump Na+out of the cell and K+in.生理条件生理条件温度降低温度降低液晶态液晶态晶态晶态 Dynamic nature of biomembraneThe lateral diffusion of membrane lipids can demonstrated experimentally by a technique called Fluorescence Recovery After Photobleaching(FRAP).2 Figure

15、 10-34.Experiment demonstrating the mixing of plasma membrane proteins on mouse-human hybrid cells.The mouse and human proteins are initially confined to their own halves of the newly formed heterocaryon plasma membrane,but they intermix with time.The two antibodies used to visualize the proteins ca

16、n be distinguished in a fluorescence microscope because fluorescein is green whereas rhodamine is red.(Based on observations of L.D.Frye and M.Edidin,J.Cell Sci.7:319-335)Figure 10-35.Antibody-induced patching and capping of a cell-surface protein on a white blood cell.The bivalent（二价的）antibodies cr

17、oss-link the protein molecules to which they bind.This causes them to cluster into large patches,which are actively swept to the tail end of the cell to form a cap.The centrosome,which governs the head-tail polarity of the cell,is shown in orange.Figure 10-37.Diagram of an epithelial cell showing ho

18、w a plasma membrane protein is restricted to a particular domain of the membrane.Protein A(in the apical membrane)and protein B(in the basal and lateral membranes)can diffuse laterally in their own domains but are prevented from entering the other domain,at least partly by the specialized cell junct

19、ion called a tight junction.Lipid molecules in the outer(noncytoplasmic)monolayer of the plasma membrane are likewise unable to diffuse between the two domains;lipids in the inner(cytoplasmic)monolayer,however,are able to do so.Figure 10-38.Three domains in the plasma membrane of guinea pig sperm de

20、fined with monoclonal antibodies.A guinea pig sperm is shown schematically in(A),while each of the three pairs of micrographs shown in(B),(C),and(D)shows cell-surface immunofluorescence staining with a different monoclonal antibody(on the right)next to a phase-contrast micrograph(on the left)of the

21、same cell.The antibody shown in(B)labels only the anterior head,that in(C)only the posterior head,whereas that in(D)labels only the tail.(Courtesy of Selena Carroll and Diana Myles.)Figure 10-39.Four ways in which the lateral mobility of specific plasma membrane proteins can be restricted.The proteins can self-assemble into large aggregates(such as bacteriorhodopsin in the purple membrane of Halobacterium)(A);they can be tethered by interactions with assemblies of macromolecules outside(B)or inside(C)the cell;or they can interact with proteins on the surface of another cell(D).P95