Download （2）membrane protein accomplish a lot of important membrane

第二篇 细胞的结构与功能
Cellular structures and their functions
Location, structure
Molecular components
Function
Life activity of cell and life phenomena
To be simplified: birth, aging, illness and death
Including: cell differentiation, growth and division, mobility,
inheritance and mutation, metabolisms in energy and material, response to
stimuli from outside the cell, cell senescence and death.
具体说包括细胞的分化、生长与分裂、细胞的运动、遗传与变异、细胞的
物质与能量代谢、细胞对外界刺激的应答、细胞的衰老与死亡。
Part II Cellular structure
and their functions
Cell membrane and transmembrane transportation
Endomembrane system and vesicle transport
Mitochondria and energy transformation
Nuclei
Cytoskeleton and cell movement
Cell junctions and cell adhesion
Extracellular matrix and its functions
Chapter 4. Cell membrane and
transmembrane transportation
Chemical components of membrane
Across membrane transport of small molecules
Cell membrane
Across membrane transport of large molecules
and particles
Cell surface and its specified structure
Abnormality of cell membrane and diseases
Section 1. Chemical components of cell
Membrane and their molecular structure
1.Chemical components of cell membrane
（1）lipids constitute the skeleton of the membrane
phospholipids
膜脂（membrane lipid） cholesterol
glycolipid
Section 1. Chemical components of cell
Membrane and their molecular structure
1.Chemical components of cell membrane
（1）lipids constitute the skeleton of the membrane
phospholipids
膜脂（membrane lipid） cholesterol
glycolipid
PE
PS
Figure 10-3 Molecular Biology of the Cell (© Garland Science 2008)
PC
PE
PS
Figure 10-3 Molecular Biology of the Cell (© Garland Science 2008)
PC
PE
PS
Figure 10-3 Molecular Biology of the Cell (© Garland Science 2008)
PC
PE
PS
Figure 10-3 Molecular Biology of the Cell (© Garland Science 2008)
PC
Figure 10-18 Molecular Biology of the Cell (© Garland Science 2008)
Figure 10-4 Molecular Biology of the Cell (© Garland Science 2008)
phospholipids：basic components，50%
Membrane
lipid
Cholesterol :stabilize membrane structure and
modulate the fluidity of membrane
glycolipid：5% or less，located outer layer of
membrane
Figure 10-5 Molecular Biology of the Cell (© Garland Science 2008)
Figure 10-3. A lipid micelle and a lipid bilayer seen in cross-section.
Lipid molecules form such structures spontaneously in water. The shape
of the lipid molecule determines which of these structures is formed.
Wedge-shaped lipid molecules (above) form micelles, whereas cylindershaped phospholipid molecules (below) form bilayers.
Figure 10-11 Molecular Biology of the Cell (© Garland Science 2008)
Figure 10-12 Molecular Biology of the Cell (© Garland Science 2008)
The importance of the lipid
bilayer
• The lipids of a membrane are more than
simple structural elements:
• It is a skeleton of the membrane
• Lipid composition can determine the physical
state of the membrane and influence the activity
of particular membrane proteins.
• Membrane lipids also provide the precursors for
highly active chemical messengers that regulate
cellular function.
Figure 10-1c Molecular Biology of the Cell (© Garland Science 2008)
（2）membrane protein accomplish a lot of
important membrane functions
内在膜蛋白（intrinsic membrane protein）
整合膜蛋白（integral membrane protein）
Membrane
Proteins
外在膜蛋白(extrinsic membrane protein)
外周蛋白（peripheral protein）
脂锚定蛋白（lipid anchored protein)
脂连接蛋白（lipid-linked protein）
（3）sugar-chains from glycoproteins and
Glycolipids cover the cell surface
2. Characteristics of the cell membrane
1. Asymmetry of lipids
（1）membrane
asymmetry
2. Asymmetry of proteins
3. Asymmetry of sugar-chains
（2）Fluidity of the membrane guaranteed the
biological functions of the membrane
1. Lipid layer is a two dimentaional fluid
液晶态（liquid-crystal state)
2. Membrane lipids have different movements
3. Many factors impacting the fluidity of the lipids
（1）the saturation of the fatty chain
（2）the length of the fatty chain
（3）cholesterol
T >phase-transition temperature,
reducing fluidity
T <phase-transition temperature
Increasing fluidity
（4）the ratio of phosphotidal choline(PC) and
sphingomylin(SM)
（5）membrane proteins
相变温度的概念
4. The movement of lipid proteins
（1）lateral diffusion
（2）rotation
3. Molecular models of cell membrane
The pioneer researchers were E. Gorter and Grendel
Blood ghost: red blood cell membrane
（1）Sandwish model
To account for permeability of membrane to
non-lipid substances, Danielli and Davson proposed
sandwich model (later proved wrong) with
phospholipid bilayer between layers of protein.
（2）unit membrane model
20C.C 50’s J.D Robertson
（三）流动镶嵌模型
fluid-mosaic model
• In 1972, Singer and Nicolson introduced the
currently accepted fluid-mosaic model of
membrane structure.
• In this model, a flexible layer made of lipid molecules is
interspersed with large protein molecules that act as channels,
transporters through which other molecules enter and leave
the cell. There are also receptors in the membrane.
– The core lipid bilayer exists in a fluid state, capable of
dynamic movement.
– Membrane proteins form a mosaic of particles penetrating
the lipid to varying degree
The model described the fluidity and
asymmetry of the membrane
1975年 D.F Wallach 提出了一种“晶格镶嵌模型” （crystal mosaic model)
1977年M.KJain 和H.B White 又提出了“板块镶嵌模型”（block mosaic mode
（4）lipid
raft（严格说，它不是模型而是一种特殊的结构）
Chaper 2 membrane transport
of small molecules
1. Selective permeability and
simple diffusion
2.Transport protein mediated
transportation of small molecules
Carrier Protein
膜转运蛋白（membrane transport protein）
Channel Protein
（1）ion channels transporting various ions
Passive transport
Ion channel
Specificity for the ion size and charge
High speed of transporting , 106 to 108 /second
Conformation changes from opening to closing
K+ channel constitutively opens，
while most channels are gated opening
Figure 11-31 Molecular Biology of the Cell (© Garland Science 2008)
（1）carrier protein mediated
facilitated diffusion
（3）carrier protein mediated
positive transport
1. Ion pump hydrolyze ATP for active
transport
钙泵
2. ion-driven cotransporters
Cotransport: coupled transport
A special kind of active
transport
• Two molecules travel together, one as a
passenger, the other as a driver. The
driver diffuses down its electrochemical
gradient, but it cannot do so unless it has
the passenger.
• ATP is not directly involved, but it sets up
the electrochemical gradient used to
propel the driver.
• Symport
•
The passenger and the driver are
transported in the same direction.
• Na-glucose symport takes place in the
intestine, from the gut lumen to the insides of
the cells lining the gut.
• Antiport
• The driver and passenger travel in
opposite directions.
Na+-H+ exchange carrier
Cl--HCO3- exchanger
• The energy of ATP may be used directly or indirectly.
• Direct Active Transport. Some transporters bind ATP directly and use the
energy of its hydrolysis to drive active transport.
• Indirect Active Transport. Other transporters use the energy already stored in
the gradient of a directly-pumped ion. Direct active transport of the ion
establishes a concentration gradient. When this is relieved by facilitated
diffusion, the energy released can be harnessed to the pumping of some other
ion or molecule.
Chapter 3. membrane transport of big
molecules and particles
Bacteria
Endocytosis
Exocytosis
1. Endocytosis
（1） phagocytosis
吞噬作用
A. Phagocytosis
• Cell eating: cells engulf particles with
pseudopodia and pinches off a food vacuole.
• Two examples:
1. White Blood Cell
2. Amoeba
Bacteria
White Blood Cell
Phagocytosis: The uptake of large particles
Including: macromolecules,
cell debris, even microorganisms
and other cells.
Phagocytosis is usually
restricted to specialized cells
called Phagocytes.
Phagocytosis is initiated by
cellular contact with an
appropriate target.
Phagocytosis may be
stimulated by the opsonins
Phagocytosis is driven by
contractile activities of MF.
（2）Pinocytosis
胞饮作用
B. Pinocytosis
• Cell drinking: droplets of extracellular fluid
are absorbed into the cell by small vesicles.
• Example:
Food Particles
（3）Receptor mediated endocytosis
C. Receptor-Mediated Endocytosis
• Importing specific macromolecules (hormones)
into the cell by the inward budding of vesicles
formed from coated pits (receptors).
Liver Cell
Hormones
Receptors
• In most animal cells, clathrin-coated pits
and vesicles provide an efficient pathway
for taking up specific macromolecules from
the extracellular fluid. In this process the
macromolecules bind to complementary
transmembrane receptor proteins,
accumulate in coated pits, and then enter
the cell as receptor-macromolecule
complexes in clathrin-coated vesicles.
• Receptor-mediated endocytosis provides a
selective concentrating mechanism that
increases the efficiency of internalization
of particular ligands more than a
hundredfold, so that even minor
components of the extracellular fluid can
be specifically taken up in large amounts
without taking in a correspondingly large
volume of extracellular fluid.
clathrin
2. Excytosis(胞吐作用)
（一）结构性分泌途径（constitutive secretion pathway)
（二）条件性分泌途径（regulated secretion pathway)
Chapter4 .cell surface and specified structures
1. Cell coat or glycocalyx
(细胞外被和胞质溶胶)
2.Specified cell surface
1.Microvillus(微绒毛)
2. Cilia and flagella(纤毛与鞭毛)
trachea
3. 褶皱（ruffe)或片状伪足（lamellipodium)
Chapter 5 membrane abnormality and
diseases
1. The abnormality of carrier protein and
diseases
1. 胱氨酸尿症（cystinuria)
膜转运体异常疾病，遗传性
病人肾小管上皮转运胱氨酸及二氨基氨基酸（赖氨酸，精氨酸
及鸟氨酸）的载体蛋白缺陷而 引起的疾病。
pH5-7 时，胱氨酸的饱和浓度为0.3-0.4g/L
2. 肾性糖尿（renal glycosuria)
2. Abnormality of ion channels and diseases
Cystic fibrosis， CF
3. Abnormality of membrane receptor and diseases
(1). 家族性高胆固醇血症（familial hypercholesterolemina)
(2). 重症肌无力（myasthenia gravis)
自身免疫疾病， 体内产生了抗N-Ach 受体的抗体。
2. 重症肌无力（myasthenia gravis)
自身免疫疾病， 体内产生了抗N-Ach 受体的抗体。
. Cancer and cell surface changes
(癌变和细胞表面的关系)
（1）contact and
grow inhibition loss
接触抑制丧失
（2）abnormality of membrane
components(细胞的组成异常)
膜脂的改变：Gm3
Gd3
膜蛋白的改变
（3）surface antigen change抗原性的改变
（4）the change of reactions with extracellular
lectins(与外源性凝集素的反应)
Summery ：
Chemical
components
model
Simple diffusion自由扩散
passive
Ion channels 离子通道
Carrier protein mediated
facilitated diffusion载体介导的易化
扩散
Ion pump 离子泵
Small molecule
transport
active（载体介导运输）
Cotransport
协同运输
symport
antiport
excytosis
phagocytosis
Large molecule
and particle
transport
endocytosis pinocytosis
Receptor mediated endocytosis
Cell surface： 细胞外被（cell coat）或糖萼（ glycocalyx）
Specified cell
surface structure
细胞表面的特化结构
microvillus
Cillia or flagella
Ruffle or lamellipodium
Cell membrane and diseases
细胞膜与疾病