? E1.Membrane lipids
? E2.Membrane protein and carbohydrate
? E3.Membrane transport:small molecules
? E4.Membrane transport:macromolecules
? E5.Signal transduction
E Membranes
Membranes
Membrane lipids
Fatty acid chains
Lipid bilayer
Membrane fluidity
Fluid mosaic model of membrane structure
E1 Membrane lipids
Membrane
? Membranes form boundaries around the cell
and around distinct subcellular
compartments,
? They act as selectively permeable barriers
and are involved in signaling processes,
? All membranes contain varying amounts of
lipid and protein and some contain small
amounts of carbohydrate,
Membrane
Membrane lipids
Three major classes of lipids,
1,The glycerophospholipids,甘油磷脂
2,The sphingolipids鞘脂
3,The sterols胆固醇
Membrane lipids
Triacylglycerol三酰甘油
Phosphatidylcholine磷脂酰胆碱
Phosphatidate
Glycerophospholipids
Sphingolipids
Cerebroside脑苷脂
Cholesterol
Cholesterol
Lipid bilayer
Bilayer
Lipid bilayer
Lipid bilayers
Membrane fulidity
Fluid mosaic model
1,Integral membrane proteins Integral
membrane protein movement and distribution
2,Membrane protein purification and
reconstitution
3,Peripheral membrane proteins
4,Membrane carbohydrate
E2 Membrane protein and carbohydrate
Integral membrane proteins
? Glycophorin
? Multiple membrane-spanning proteins
? Lipid-anchored proteins
Bacteriorhodopsin
Integral membrane protein
Membrane protein
Membrane protein
Membrane protein
Integral membrane protein
movement and distribution
? That proteins are free to move laterally in the plane
of the bilayer was shown by fusing cultured mouse
cells with human cells to form a hybrid cell known as
a heterokaryon
? Two kinds of cells were labeled with green-
fluorescing and red-fluorescingdye respectively,
See Fig3.a pp128
? The distribution of proteins in membrane can be
revealed by electron microscopy using the freeze-
fracture technique
Membrane protein purification
and reconstitution
? The first step in the purification is the disruption
of the membrane structure by solubilizing it with
a detergent,
? It is coated with a layer of amphipathic detergent
molecules,allowing the protein to remain in
aqueous solution and be purified as for a soluble
globular protein,
? Then can be reincorporated into artificial lipid
vesicles,
Protein purification
Membrane protein separation
Process of disruption
? Fig5 shows the process of disruption,
? If phospholipids are add to the protein in
detergent solution and the detergent dialyzed
away,phospholipid vesicles containing the
protein will spontaneously form,
Peripheral membrane proteins
? Loosely bound to the membrane
? It can be removed readily
Peripheral membrane proteins
? Peripheral membrane proteins are less tightly
bound to the lipid bilayer than integral
membrane proteins and can be readily removed
by washing the membranes with a solution of
high ionic strength or high pH,
? No part of a peripheral membrane protein
interacts with the hydrophobic core of the
membrane
Peripheral membrane porteins
Membrane carbohydrate
? Sugar residues are found only on the
extracellular side of the plasma membrane
attached either to lipids to form glycolipids or
to proteins to form glycoproteins,
Signal
? Membrane permeability
? Passive transport
? Active transport
? Glucose transport into intestinal epithlial
cells
E3 Membrane transport
Membrane permeability
Passive transport
Glucose transport
Glucose transport
Active transport
Na pump
ATPase
4 Classes of transport ATPases
Co-transport
Co-transport
Cotransport
Summary of transport type
Glucose transport into intestinal
epithlial cells
Epithlial cell
Proton pump
? Exocytosis
? Endocytosis
? Phagocytosis
? Pinocytosis
? receptor-mediated endocytosis
? Clathrin-coated pits and vesicles
E4 Membrane transport,
macromolecules
Exocytosis
Endocytosis
Endoexo
Phagocytosis
Pinocytosis
Receptor-mediated endocytosis
Receptor-mediated endocytosis
Clathrin-coated pits and vesicles
? Both endocytosis of material at the plasma
membrane and exocytosis from the Golgi
apparatus involve the formation of clathrin-
coated pits and vesicles,
? On the cytosolic side of the membrane these
structures have an electron-dense coat
consisting mainly of the protein clathrin,the
polypeptides of which form a three-legged
structure known as a triskelion,
Clathrin-coated pits and vesicles
? The clathrin triskelions assenble into a
basket-like convex framework that causes
the membrane to invaginate clathrin-coated
vesicles migrate into the cell where the
clathrin coats are lost before delivering their
contents to the lysosomes,
? Cell signaling
? Hormones
? Cell-surface receptors
? Second messengers
E5 Single transduction
Cell signaling
? Cells communicate with one another in multicellular
organisms using extracellular signaling molecules or
hormones,
? The hormone is secreted by the signaling cell and
then binds to a receptor on the target cell,initiating
a response in that cell,
? In endocrine signaling the hormone acts at a distant
site in the body from where it was produced,in
paracrine signaling the hormone acts on nearby
cells,and in autocrine signaling the hormone acts on
the same cell from which it was secreted,
Endocrine
Paracrine
Hormones
? Some lipophilic hormones diffuse across the
plasma membrane and interact with
intracellular receptors in the cytosol or
nucleus,Other lipophilic hormones and
hydrophilic hormones bind to receptor
proteins in the plasma membrane,
Cell-surface receptors
? Cell-surface receptors are integral membrane
proteins located in the plasma membrane that
bind the hormone with high affinity and
specificity,
? On binding the ligand,the receptor undergoes
a conformational change and transmits the
information into the cell,
Cell-surface receptors
? G protein-linked receptors activate G
proteins that in turn lead to the
production of an intracellular second
messenger
Enzyme-liked receptor
Ion channel-linked receptor
G protein-linked receptor
Cell-surface receptors
G protein cycle
Second messengers
? Intracellular signaling molecules are
produced in response to the activation of G
proteins by cell-surface receptors,
? The second messengers cAMP and 3 ′ 5 ′ -
cyclic guanosine monophosphate are
produced by adenylate cyclase and
guanylate cyclase,recepctively,
cAMP
cAMP
G-protein turns on adenylyl cyclase
adenylyl cyclase produces cAMP
cAMP binds to target and turns it on
IP3(Ca2+)
IP3
DAG
? E2.Membrane protein and carbohydrate
? E3.Membrane transport:small molecules
? E4.Membrane transport:macromolecules
? E5.Signal transduction
E Membranes
Membranes
Membrane lipids
Fatty acid chains
Lipid bilayer
Membrane fluidity
Fluid mosaic model of membrane structure
E1 Membrane lipids
Membrane
? Membranes form boundaries around the cell
and around distinct subcellular
compartments,
? They act as selectively permeable barriers
and are involved in signaling processes,
? All membranes contain varying amounts of
lipid and protein and some contain small
amounts of carbohydrate,
Membrane
Membrane lipids
Three major classes of lipids,
1,The glycerophospholipids,甘油磷脂
2,The sphingolipids鞘脂
3,The sterols胆固醇
Membrane lipids
Triacylglycerol三酰甘油
Phosphatidylcholine磷脂酰胆碱
Phosphatidate
Glycerophospholipids
Sphingolipids
Cerebroside脑苷脂
Cholesterol
Cholesterol
Lipid bilayer
Bilayer
Lipid bilayer
Lipid bilayers
Membrane fulidity
Fluid mosaic model
1,Integral membrane proteins Integral
membrane protein movement and distribution
2,Membrane protein purification and
reconstitution
3,Peripheral membrane proteins
4,Membrane carbohydrate
E2 Membrane protein and carbohydrate
Integral membrane proteins
? Glycophorin
? Multiple membrane-spanning proteins
? Lipid-anchored proteins
Bacteriorhodopsin
Integral membrane protein
Membrane protein
Membrane protein
Membrane protein
Integral membrane protein
movement and distribution
? That proteins are free to move laterally in the plane
of the bilayer was shown by fusing cultured mouse
cells with human cells to form a hybrid cell known as
a heterokaryon
? Two kinds of cells were labeled with green-
fluorescing and red-fluorescingdye respectively,
See Fig3.a pp128
? The distribution of proteins in membrane can be
revealed by electron microscopy using the freeze-
fracture technique
Membrane protein purification
and reconstitution
? The first step in the purification is the disruption
of the membrane structure by solubilizing it with
a detergent,
? It is coated with a layer of amphipathic detergent
molecules,allowing the protein to remain in
aqueous solution and be purified as for a soluble
globular protein,
? Then can be reincorporated into artificial lipid
vesicles,
Protein purification
Membrane protein separation
Process of disruption
? Fig5 shows the process of disruption,
? If phospholipids are add to the protein in
detergent solution and the detergent dialyzed
away,phospholipid vesicles containing the
protein will spontaneously form,
Peripheral membrane proteins
? Loosely bound to the membrane
? It can be removed readily
Peripheral membrane proteins
? Peripheral membrane proteins are less tightly
bound to the lipid bilayer than integral
membrane proteins and can be readily removed
by washing the membranes with a solution of
high ionic strength or high pH,
? No part of a peripheral membrane protein
interacts with the hydrophobic core of the
membrane
Peripheral membrane porteins
Membrane carbohydrate
? Sugar residues are found only on the
extracellular side of the plasma membrane
attached either to lipids to form glycolipids or
to proteins to form glycoproteins,
Signal
? Membrane permeability
? Passive transport
? Active transport
? Glucose transport into intestinal epithlial
cells
E3 Membrane transport
Membrane permeability
Passive transport
Glucose transport
Glucose transport
Active transport
Na pump
ATPase
4 Classes of transport ATPases
Co-transport
Co-transport
Cotransport
Summary of transport type
Glucose transport into intestinal
epithlial cells
Epithlial cell
Proton pump
? Exocytosis
? Endocytosis
? Phagocytosis
? Pinocytosis
? receptor-mediated endocytosis
? Clathrin-coated pits and vesicles
E4 Membrane transport,
macromolecules
Exocytosis
Endocytosis
Endoexo
Phagocytosis
Pinocytosis
Receptor-mediated endocytosis
Receptor-mediated endocytosis
Clathrin-coated pits and vesicles
? Both endocytosis of material at the plasma
membrane and exocytosis from the Golgi
apparatus involve the formation of clathrin-
coated pits and vesicles,
? On the cytosolic side of the membrane these
structures have an electron-dense coat
consisting mainly of the protein clathrin,the
polypeptides of which form a three-legged
structure known as a triskelion,
Clathrin-coated pits and vesicles
? The clathrin triskelions assenble into a
basket-like convex framework that causes
the membrane to invaginate clathrin-coated
vesicles migrate into the cell where the
clathrin coats are lost before delivering their
contents to the lysosomes,
? Cell signaling
? Hormones
? Cell-surface receptors
? Second messengers
E5 Single transduction
Cell signaling
? Cells communicate with one another in multicellular
organisms using extracellular signaling molecules or
hormones,
? The hormone is secreted by the signaling cell and
then binds to a receptor on the target cell,initiating
a response in that cell,
? In endocrine signaling the hormone acts at a distant
site in the body from where it was produced,in
paracrine signaling the hormone acts on nearby
cells,and in autocrine signaling the hormone acts on
the same cell from which it was secreted,
Endocrine
Paracrine
Hormones
? Some lipophilic hormones diffuse across the
plasma membrane and interact with
intracellular receptors in the cytosol or
nucleus,Other lipophilic hormones and
hydrophilic hormones bind to receptor
proteins in the plasma membrane,
Cell-surface receptors
? Cell-surface receptors are integral membrane
proteins located in the plasma membrane that
bind the hormone with high affinity and
specificity,
? On binding the ligand,the receptor undergoes
a conformational change and transmits the
information into the cell,
Cell-surface receptors
? G protein-linked receptors activate G
proteins that in turn lead to the
production of an intracellular second
messenger
Enzyme-liked receptor
Ion channel-linked receptor
G protein-linked receptor
Cell-surface receptors
G protein cycle
Second messengers
? Intracellular signaling molecules are
produced in response to the activation of G
proteins by cell-surface receptors,
? The second messengers cAMP and 3 ′ 5 ′ -
cyclic guanosine monophosphate are
produced by adenylate cyclase and
guanylate cyclase,recepctively,
cAMP
cAMP
G-protein turns on adenylyl cyclase
adenylyl cyclase produces cAMP
cAMP binds to target and turns it on
IP3(Ca2+)
IP3
DAG
