Integral proteins are in

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Chapter 4
Biomembranes: Their Structure,
Chemistry and Functions
Learning objectives:
1. A brief history of studies on the structrure of the
plasma membrane
2. Model of membrane structure: an experimental
perspective
3. The chemical composition of membranes
4. Characteristics of biomembrane
5. An overview of the functions of biomembranes
1. A brief history of studies
on the structrure of the
plasmic membrane
A. Conception:
Plasma membrane(cell membrane),
Intracellular membrane,
Biomembrane.
B. The history of study
Overton(1890s):
Lipid nature of PM;
Gortter and Grendel(1925):
The basis of membrane structure is a lipid bilayer
To answer the question that how many lipid layers were in
membrane, in 1925 Gorter and Grendel extracted the lipids
from a known number of erythrocytes and spread the lipid
film on a water surface. The area of lipid film on the water
was about twice(1.8-2.2) the estimated total surface area of the
erythrocytes, so they concluded that the erythrocyte plasma
membrane consisted of not one but two layers of lipids.
Cell physiologists(1920s and 1930s) :
The decrease in surface tensions of PM might be explained by
the proteins.
H.Davson and J.Danielli(1935): “sandwich model”
Membranes also contain proteins.
If the membranes only consist of pure lipids, it could not explain
all the properties of membranes. For example, sugars, ions, and
other hydrophilic solutes move into and out of cells much more
readily than could be explained by the permeability of pure lipid
bilayers. To explain such differences, Davson and Danielli
invoked the presence of proteins in membranes in 1935.
The plasma membrane is composed of a lipid bilayer that is
lined on both its inner and outer surface by a layer of globular
proteins; in addition to , the presence of protein-lined pores for
polar solutes and ions to enter and exit the cell.
 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;
Functional rafts in Cell
membranes.
Nature 387:569-572
2. Singer and Nicolson’s Model of membrane
structure: The fluid-mosaic model is the “central
dogma” of membrane biology.
A. The core lipid bilayer exists in a fluid state, capable
of dynamic movement.
B. Membrane proteins form a mosaic of particles
penetrating the lipid to varying degrees.
The Fluid Mosaic
Model, proposed in
1972 by Singer and
Nicolson, had two
key features, both
implied in its name.
3. The chemical composition of membranes
A. Membrane Lipids: The Fluid Part of the Model
Membrane lipids are amphipathic.
There are three major classes of lipids:
Phospholipids:
Phosphoglyceride and sphingolipids
Glycolipids
Sterols ( is only found in animals)
Three kinds of movement of Membrane lipids
Three kinds of movement:
Rotation about its long axis;
Lateral diffusion by
exchanging places;
Transverse diffusion, or
“flip-flop” from one
monolayer to the other.
Flippases catalyze the flipflop.
The effects of fatty acid composition on
membrane fluidity
The length of the fatty acid
The degree of unsaturation of their side chains
The temperature.
The effects of sterols on membrane fluidity
Liposome
and
application
Study on nature; gene transfer; as a carrier.
B. Membrane Proteins:
The “Mosaic” Part of the Model
Membranes contain integral, peripheral, and
lipid-anchored proteins:
lipid-anchored proteins
Rolled-up  sheet
 helix
Amphipathic  helix
Noncovalent interactions
 Integral proteins are amphipathic, with
hydrophobic domains anchoring them in the bilayer
and hydrophilic regions forming functional domains
outside of the bilayer.
 Channel proteins have hydrophilic cores that form
aqueous channels in the membrane-spanning region.
 Peripheral proteins are attached to the membrane
by weak bonds and are easily solubilizad.
 Lipid-attachored membrane proteins are
distinguished by both the types of lipid anchor and
their orientation.
Proteins can be seperated by SDS-polyacrylamide
gel electrophoresis
The orientation of integral proteins can be
determined using nonpenetrating agents that label
the proteins.
Identification of transmembrane domains can be
predicted from the amino acid sequence using a
hydropathy plot.
Membrane domains and polarity.
Protein/lipid ratios vary considerably among
different membrane types.
Lipid and protein components of membranes
are bound together by non-covalent forces.
Detergent--- small amphipathic molecules
Integral proteins are embedded in the membrane;
their removal requires detergents.
CH3-(CH2)11-OSO3-Na+
SDS:
Triton X-100:
CH3
CH3
CH3 – C – CH2 – C –
CH3
CH3
(O-CH2-CH2)10- OH
C. Membrane Carbohydrates
Membrane contain carbohydrates convalently
linked to lipids and proteins on the extracellular
surface of the bilayer.
Glycoproteins have short , branched
carbohydrates for interactions with other cells and
structures outside the cell.
Glycolipids have larger carbohydrate chains that
may be cell-to-cell recognition sites.
4. Characteristics of biomembrane
A. Dynamic nature of biomembrane
Fluidity of membrane lipid. It give
membranes the ability to fuse, form networks,
and separate charge;
Motility of membrane protein.
The lateral diffusion of membrane lipids can demonstrated
experimentally by a technique called Fluorescence Recovery After
Photobleaching (FRAP).
B. The asymmetry of biomembranes
—The foundation of membrane function
 The asymmetry of membrane lipids and glycolipids :
The inner and outer membrane leaflets were shown to
have different lipid compositions.
 Lipld asymmentry gives the
membrane leaflets different
physical and chemical
properties appropriate for the
different interactions occurring
at the two membrane faces.
The asymmetric distribution of PL in HE
The asymmetry of membrane protein
and glycoprotein :
Integral proteins attach to the bilayer asymmetrically, giving
the membrane a distinct “sidedness”.
The membrane carbohydrates only distributing on ES face.
 Integral proteins have orientation within Membranes.
 The distribution of
integral proteins can
be analyzed by
freeze-fracture and
freeze-etching
techniques.
C. The inhomogeneity of membranes
 Lipid composition can influence the activity of
membrane proteins and determine the physical state
of the membrane.
Biomembrane have agglomeration
Model of
Lipid raft in
TGN
5. An Overview of membrane functions
1. Define the
boundaries of the cell
and its organelles.
2. Serve as loci for
specific functions.
3. provide for and
regulate transport
processes.
4. contain the receptors
needed to detect
external signals.
5. provide mechanisms
for cell-to-cell contact,
communication and
adhesion
A. PM define the boundaries of the cell and
organelles.
B. Compartmentalization: membranes form
continuous sheets that enclose intracellular
compartments.
C. Transporting solutes: membrane proteins
facilitate the movement of substances between
compartments.
D. Responding to external signals: membrane
receptors transduce signals from outside the
cell in response to specific ligands.
E. Intercellular interaction: membrane
mediate recognition and interaction between
adjacent cells by cell-to-cell communication
and junction.
F. Locus for biochemical activities: membrane
provide a scaffold that organizes enzymes for
effective interaction.
G. Energy transduction: membranes
transduce photosynthetic energy, convert
chemical energy to ATP, and store energy in
ion and solute gradients.
Analysis of membrane proteins by using of
molecule biological technique
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