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Contents
1
...
Functions of the Plasma Membrane
3
...
Major lipids
5
...
Fluidity of the bilayer
7
...
Lipid droplets
9
...
Types of Membrane Proteins
11
...
Peripheral Membrane Proteins
13
...
Action of detergents on membrane proteins
15
...
Large protein complexes
17
...
Protein and lipid domains within the membrane
19
...
Bilayer deformation by membrane proteins
21
...


1
...




It surrounds the cells and the organelles enclosed within them
...




PM is around 5-10 nm wide and is extremely thin
...




Despite the functional differences, the PMs share a fundamental feature
...




This lipid bilayer provides the basic fluid structure of the PM and serves as a
relatively impermeable barrier to the passage of most water-soluble molecules
...


2
...
g
...
These compartments
are formed by the PMs that surround them)
...


Scaffold for biochemical activities


Membranes carry the proteins and other components that are crucial for certain
biochemical activities such as ATP synthesis, Ion transport etc
...


Selective Permeability


PMs prevent unrestricted exchange of molecules between the 2 sides of the
membrane
...




Hence, PMs are responsible for the movement of selective molecules
...




They allow the cells to accumulate substances needed for forming biomolecules
such as sugars, amino acids, lipids etc
...


Signal Transduction


The plasma membrane plays a pivotal role in signal transduction
...




Different types of cells have membranes with different receptors and are,
therefore, capable of recognizing and responding to different environmental
stimuli
...
(For example, signals generated at the plasma membrane may tell a cell to
manufacture more glycogen, to prepare for cell division, to move toward a higher
concentration of a particular compound, to release calcium from internal stores, or
possibly to commit suicide (apoptosis)
...




Proteins within the plasma membrane may also facilitate the interaction between
extracellular materials and the intracellular cytoskeleton
...




The most fundamental energy transduction occurs during photosynthesis when
energy in sunlight is absorbed by membrane‐bound pigments, converted into
chemical energy, and stored in carbohydrates
...




In eukaryotes, the machinery for these energy conversions is contained within
membranes of chloroplasts and mitochondria
...
COMPONENTS OF THE PLASMA MEMBRANE
Lipids


Lipid molecules constitute about 50% of the mass of most animal cell membranes
...




The lipid bilayer serves primarily as a structural backbone of the membrane and
provides the barrier that prevents random movements of water‐soluble materials
into and out of the cell
...




Fluidity is a critical property of the PM and is determined by both temperature and
lipid composition
...




All of the lipid molecules in cell membranes are amphiphilic—that is, they have a
hydrophilic (“water-loving”) or polar end and a hydrophobic (“water-fearing”) or
nonpolar end
...




Different PMs carry different proteins
...




Therefore, proteins provide each PM with characteristic properties
...




This asymmetry is referred to as membrane “sidedness
...
g
...




The amounts and types of proteins in a membrane are highly variable
...




Contrastingly, in the membranes involved in ATP production (such as the
internal membranes of mitochondria and chloroplasts), approximately 75% is
protein
...


Carbohydrates


Eukaryotic PMs also carry carbohydrates in addition to lipids and proteins
...




90% of the PM carbs are present as glycoproteins
...




All the carbs of the PM face the extracellular space
...




Glycosylation is the most complex of all protein modifications
...




In contrast to most high‐molecular‐weight carbohydrates (such as glycogen,
starch, or cellulose), which are polymers of a single sugar, the oligosaccharides
attached to membrane proteins and lipids can display extensive variability in
composition and structure
...




Oligosaccharides may be attached to several different amino acids by two major
types of linkages
...




The carbohydrates of the glycolipids of the red blood cell plasma membrane
determine a person’s blood type
...
MAJOR LIPIDS


Phospholipids are the major lipids found in the PM
...




In animal, plant and bacterial cells, the tails are usually fatty acids of differing
lengths
...




The other tail is saturated
...




Differences in the length and saturation of these fatty acid tails determine how the
phospholipids pack against one another
...







They carry a 3-Carbon glycerol backbone
...

The last carbon atom is bound to the head group
...

Phosphatidylethanolamine, Phosphatidylserine and Phosphatidylcholine are the
major Phosphoglycerides
...












Sphingolipids have a sphingosine backbone that carries a long acyl chain with a
NH2 and 2 OH groups at one end
...

Sphingomyelin is the most common type of sphingolipid that carries a fatty acid
chain attached to the amino group and a phosphocholine attached to the terminal
OH group
...

Together, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine
and sphingomyelin constitute the major phospholipids of the PM
...






Glycolipids are sugar-containing lipids
...

In animal cells, glycolipids are made from sphingosine
...

This ability to self-associate helps them to preferentially occupy locations within
the lipid rafts
...

The lumen is topologically equivalent to the membrane
...

Glycolipids occur in most eukaryotic PMs constituting around 5% of the total lipid
composition
...

Gangliosides contain oligosaccharides with 1/2 sialic acid moieties which confers
a negative charge on the gangliosides
...

The most abundant type of gangliosides is found in the PM of nerve cells
...

The functions of glycolipids are determined by their localization
...
the epithelial cells are exposed to
...
alteration
...

Humans who are unable to synthesize a particular ganglioside (GM3) suffer from
a serious neurological disease characterized by severe seizures and blindness
...

Certain glycolipids also facilitate the entry of harmful pathogens such as bacteria,
viruses etc
...
g
...

GM1 is expressed greatly in the intestinal epithelial cells






When the cholera toxin binds to GM1, it results in the increase of intracellular
cAMP levels
...


Polyomaviruses also enter the cells by binding to ganglioside
...
BILAYER FORMATION BY THE LIPIDS









The shape and amphiphilic nature of the phospholipids enable them to
spontaneously form lipid bilayers
...

On the contrary, hydrophobic molecules do not contain any charged groups and
therefore cannot successfully establish electrostatic interactions with the water
molecules
...

This increases the release of free energy
...

Therefore, when amphiphilic molecules are dispersed in water, they aggregate in
such a way that the hydrophilic surface is exposed to the water and the
hydrophobic surface is protected from the water
...




This force that enables phospholipids to form bilayers also provides the lipid
bilayer a self-healing ability
...

This is energetically unfavorable
Therefore, the phospholipids spontaneously aggregate with one another to
eliminate the free edge
...

Individual phospholipid molecules are confined to particular spaces
...

Phospholipids are usually synthesized in the cytosolic surface
...

This is mediated by enzymes called phospholipid translocators or flippases
...

Although lipid bilayer is fluid in nature, lipid bilayers do not fuse rapidly
...

This prevents unwanted fusion between membranes and facilitates
compartmentalization
...


6
...

Certain cellular processes do not occur if the bilayer viscosity increases
...

Phase transition is the process where a membrane made of a single phospholipid
is converted from the liquid state to a crystalline state
...

A shorter chain length reduces the tendency of the hydrocarbon tails to interact
with one another, in both the same and opposite monolayer, and cis-double bonds
produce kinks in the chains that make them more difficult to pack together, so
that the membrane remains fluid at lower temperatures
...
whose temperature fluctuates depending on
their environment, frequently adjust the fatty acid position and composition to
maintain the fluidity
...
g
...

Cholesterol modulates the properties of the lipid bilayers
...





















By decreasing the mobility of the first few CH2 groups of the chains of the
phospholipid molecules, cholesterol makes the lipid bilayer less deformable in this
region and thereby decreases the permeability of the bilayer to small water-soluble
molecules
...

At the high concentrations found in most eukaryotic plasma membranes,
cholesterol also prevents the hydrocarbon chains from coming together and
crystallizing
...

Prenyl and fatty acid chains are similarly hydrophobic and flexible
...

Thus, lipid bilayers can be built from molecules with similar features but different
molecular designs
...

Analysis of membrane lipids by mass spectrometry has revealed that the lipid
composition of a typical eukaryotic cell membrane is complex
...

While some of this complexity reflects the combinatorial variation in head groups,
hydrocarbon chain lengths, and desaturation of the major phospholipid classes,
some membranes also contain many structurally distinct minor lipids, at least
some of which have important functions
...

Their local synthesis and destruction are regulated by a large number of enzymes,
which create both small intracellular signaling molecules and lipid docking sites
on membranes that recruit specific proteins from the cytosol
...
DOMAINS OF VARYING COMPOSITION WITHIN THE BILAYER




Within the lipid bilayer, different lipids aggregate to form domains
...

This domain forming ability is thought to help in concentrating membrane
proteins at specific locations for facilitating various processes such as endocytosis,
signal transduction etc
...
LIPID DROPLETS











Cells store excess lipids as lipid droplets
...

Adipocytes or fat cells have the largest number of lipid droplets
...

Other cells have smaller number of lipid droplets
...

If other cells require lipids, these lipid droplets can be accessed and they can be
transported via the bloodstream
...

These lipids do not contain hydrophilic head group and they are exclusively
hydrophobic molecules and therefore aggregate into three-dimensional
droplets rather than into bilayers
...

Some of the proteins are enzymes involved in lipid metabolism, but the
functions of most are unknown
...

They are thought to form from discrete regions of the endoplasmic reticulum
membrane where many enzymes of lipid metabolism are concentrated
...
FUNCTIONAL IMPORTANCE OF THE BILAYER’S ASSYMETRY






The lipid bilayer is asymmetric in nature i
...
the composition of the two
monolayers of the bilayer are different
...

Phosphatidylserine is negatively charged and therefore, there is considerable
difference in the charge between the two monolayers
...





Cytosolic proteins bind to the cytosolic surface of the lipid bilayer
...
g
...




Similarly, in other cases, the lipid head groups need to be modified in order to
create protein binding sites at the required time and position
...
g
...

Another example are the phospholipases such as the Phospholipase C (PLC)
which cleave certain membrane phospholipids to generate signaling
mediators
...

This asymmetry is also of great importance when distinguishing between live
and dead cells
...












This then signals immunocytes such as macrophages to phagocytose the dead
cell
...
The
phospholipid translocator that normally transports this lipid from the outer
monolayer to the inner monolayer is inactivated
...
A “scramblase” that
transfers phospholipids non-specifically in both directions between the two
monolayers is activated
...
TYPES OF MEMBRANE PROTEINS







Proteins are an important component of the PM
...

Integral membrane proteins are transmembrane proteins that span the lipid
bilayer
...
Integral proteins constitute 25–30% of all encoded proteins and roughly
60% of all current drug targets
...

Lipid-anchored proteins are the proteins that associate with the PM by binding to
lipids
...
INTEGRAL MEMBRANE PROTEINS (TRANSMEMBRANE PROTEINS)


These surface proteins function as either receptors, channels or transporters or
electron transfer agents
...

The segments of these proteins that are present within the layer are hydrophobic
in nature
...

As a result of these interactions, the selective permeability of the bilayer is
maintained, the protein is anchored within the bilayer and is also brought into
contact with the lipids that surround them
...

The portions of these proteins that project into the extra-cellular space or the
cytoplasm are hydrophilic in nature
...

A transmembrane protein always has a unique orientation in the PM
...

These domains are separated by the membrane-spanning segments of the
polypeptide chain, which contact the hydrophobic environment of the lipid
bilayer and are composed largely of amino acids with nonpolar side chains
...

The hydrogen-bonding between peptide bonds is maximized if the polypeptide
chain forms a regular α helix as it crosses the bilayer, and this is how most
membrane-spanning segments of polypeptide chains traverse the bilayer
...

An alternative way for the peptide bonds in the lipid bilayer to satisfy their
hydrogen-bonding requirements is for multiple transmembrane strands of a
polypeptide chain to be arranged as a β sheet that is rolled up into a cylinder (a socalled β barrel)
...

30 % of an organism’s proteins are transmembrane proteins
...

But multi-pass transmembrane proteins can also contain regions that fold into the
membrane from either side, squeezing into spaces between transmembrane α
helices without contacting the hydrophobic core of the lipid bilayer
...

Such regions are important for the function of some membrane proteins,
including water channel and ion channel proteins, in which the regions contribute
to the walls of the pores traversing the membrane and confer substrate specificity
on the channels
...

The sequence of the hydrophobic amino acids of these helices contains the
information that directs the protein–protein interaction
...

These interactions are crucial for the structure and function of the many channels
and transporters that move molecules across cell membranes
...

Multi-pass membrane proteins that have their transmembrane segments arranged
as β barrels rather than as α helices are comparatively rigid and therefore tend to
form crystals readily when isolated
...

These proteins are abundantly present in the membranes of bacteria,
mitochondria and chloroplasts
...

Many porin barrels are formed from a 16-strand, antiparallel β sheet rolled up into
a cylindrical structure
...
Loops of the polypeptide chain often
protrude into the lumen of the channel, narrowing it so that only certain solutes
can pass
...
coli
...

It transports iron ions across the bacterial outer membrane
...

Iron ions bind to this domain, which by an unknown mechanism moves or
changes its conformation to transfer the iron across the membrane
All β-barrel proteins are not transport proteins
...

The barrel serves as a rigid anchor, which holds the protein in the membrane and
orients the cytosolic loops that form binding sites for specific intracellular
molecules
...


Glycosylated transmembrane proteins




Many transmembrane proteins are glycosylated
...

The oligosaccharide chains of these proteins are always present on the noncytosolic side of the membrane
...

This environment decreases the likelihood that intra-chain or inter-chain
disulfide (S–S) bonds will form between cysteines on the cytosolic side of
membranes
...

Because the extracellular part of most plasma membrane proteins are glycosylated,
carbohydrates extensively coat the surface of all eukaryotic cells
...

These carbohydrates occur as oligosaccharide chains covalently bound to
membrane proteins (glycoproteins) and lipids (glycolipids)
...

Proteoglycans which consist of long polysaccharide chains linked covalently to a
protein core, are found mainly outside the cell, as part of the extracellular matrix
...

The carbohydrate layer also contains both glycoproteins and proteoglycans that
have been secreted into the extracellular space and then adsorbed onto the cell
surface
...

One of the many functions of the carbohydrate layer is to protect cells against
mechanical and chemical damage; it also keeps various other cells at a distance,
preventing unwanted cell–cell interactions
...

Although they usually contain fewer than 15 sugars, the chains are often branched,
and the sugars can be bonded together by various kinds of covalent linkages—
unlike the amino acids in a polypeptide chain, which are all linked by identical
peptide bonds
...




Both the diversity and the exposed position of the oligosaccharides on the cell
surface make them especially well-suited to function in specific cell-recognition
processes
...


12
...

It is difficult to distinguish between peripheral and integral proteins since the
integral proteins carry many polypeptide segments that might hide the
peripheral proteins
...

They stabilize the PM and anchor the integral proteins
...





13
...

The linkage is called glycosylphosphatidylinositol linkage and proteins that are
linked to the membrane in this way are called GPI-anchored proteins
...




A rare type of anemia called paroxysmal nocturnal hemoglobinuria, results from a
deficiency in GPI synthesis that makes red blood cells susceptible to lysis
...






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In some cases, myristic acid is added to the N-terminal amino group of the protein
during its synthesis
...

Membrane attachment through a single lipid anchor is not strong
...

This modification occurs in response to an extracellular signal and helps in
recruiting the protein to the surface
...




Other intracellular signaling proteins such as Ras use a combination of prenyl and
palmitic acid to be recruited to the surface
...
ACTION OF DETERGENTS ON MEMBRANE PROTEINS


Membrane proteins are not easily destructible
...




Detergents are the agents best suited for this
...




Detergents are much more soluble in water than lipids
...




At low concentration, detergents are monomeric in solution, but when their
concentration is increased above a threshold, called the critical micelle
concentration (CMC), they aggregate to form micelles
...




Both the CMC and the average number of detergent molecules in a micelle are
characteristic properties of each detergent, but they also depend on the
temperature, pH, and salt concentration
...




When mixed with membranes, the hydrophobic ends of detergents bind to the
hydrophobic regions of the membrane proteins, where they displace lipid
molecules with a collar of detergent molecules
...




Usually, some lipid molecules also remain attached to the protein
...




This allows the proteins to be analyzed by SDS polyacrylamide-gel
electrophoresis
...




These detergents cover the hydrophobic regions on membrane-spanning
segments that become exposed after lipid removal but do not unfold the
protein
...




In the presence of an excess of phospholipid molecules in such a solution,
however, membrane proteins incorporate into small liposomes that form
spontaneously
...




Membrane proteins can also be reconstituted from detergent solution into
nanodiscs, which are small, uniformly sized patches of membrane that are
surrounded by a belt of protein, which covers the exposed edge of the bilayer
to keep the patch in solution
...


15
...




The “purple membrane” of the archaeon Halobacterium salinarum is a specialized
patch in the plasma membrane that contains a single species of protein molecule,
bacteriorhodopsin
...




Each bacteriorhodopsin molecule is folded into seven closely packed
transmembrane α helices and contains a single light-absorbing group, or
chromophore (in this case, retinal), which gives the protein its purple color
...




Retinal is covalently linked to a lysine side chain of the bacteriorhodopsin protein
...




In bright light, each bacteriorhodopsin molecule can pump several hundred
protons per second
...




The energy stored in the H+ gradient also drives other energy-requiring processes
in the cell
...




The high-resolution crystal structure of bacteriorhodopsin reveals many lipid
molecules bound in specific places on the protein surface
...




The specificity of these lipid–protein interactions helps explain why eukaryotic
membranes contain such a variety of lipids, with head groups that differ in size,
shape, and charge
...




For example, rhodopsin in rod cells of the vertebrate retina and many cell-surface
receptor proteins that bind extracellular signal molecules are also built from seven
transmembrane α helices
...




Although the structures of bacteriorhodopsins and GPCRs are strikingly similar,
they show no sequence similarity and thus probably belong to two evolutionarily
distant branches of an ancient protein family
...


16
...




One is a bacterial photosynthetic reaction center, which was the first membrane
protein complex to be crystallized and analyzed by x-ray diffraction
...




The enormous photosystem II complex from cyanobacteria, for example, contains
19 protein subunits and well over 60 transmembrane helices
...


17
...




In addition, many membrane proteins are able to move laterally within the
membrane (lateral diffusion)
...
PROTEIN AND LIPID DOMAINS WITHIN THE PLASMA MEMBRANE


Most cells confine membrane proteins to specific regions in a continuous lipid
bilayer
...




In epithelial cells, such as those that line the gut or the tubules of the kidney,
certain plasma membrane enzymes and transport proteins are confined to the
apical surface of the cells, whereas others are confined to the basal and lateral
surfaces
...




The lipid compositions of these two membrane domains are also different,
demonstrating that epithelial cells can prevent the diffusion of lipid as well as
protein molecules between the domains
...




Clearly, the membrane proteins that form these intercellular junctions cannot be
allowed to diffuse laterally in the interacting membranes
...




Some of the membrane molecules are able to diffuse freely within the confines of
their own domain
...
Many other cells have similar membrane fences that
confine membrane protein diffusion to certain membrane domains
...


19
...




The characteristic biconcave shape of a red blood cell for example, results from
interactions of its plasma membrane proteins with an underlying cytoskeleton,
which consists mainly of a meshwork of the filamentous protein spectrin
...




As the principal component of the red cell cytoskeleton, it maintains the structural
integrity and shape of the plasma membrane, which is the red cell’s only
membrane, as the cell has no nucleus or other organelles
...




The fnal result is a deformable, netlike meshwork that covers the entire cytosolic
surface of the red cell membrane
...




Mice and humans with genetic abnormalities in spectrin are anemic and have red
cells that are spherical (instead of concave) and fragile; the severity of the anemia
increases with the degree of spectrin deficiency
...




This network, which constitutes the cortex of the cell, is rich in actin filaments,
which are attached to the plasma membrane in numerous ways
...




The cortex of nucleated cells also contains proteins that are structurally
homologous to spectrin and the other components of the red cell cytoskeleton
...




Because the cytoskeletal filaments are often closely opposed to the cytosolic
surface of the plasma membrane they can form mechanical barriers that obstruct
the free diffusion of proteins in the membrane
...




The barriers can be detected when the diffusion of individual membrane proteins
is followed by high-speed, single-particle tracking
...




The extent to which a transmembrane protein is confined within a corral depends
on its association with other proteins and the size of its cytoplasmic domain;
proteins with a large cytosolic domain will have a harder time passing through
cytoskeletal barriers
...




It is thought that corralling helps concentrate such signaling complexes,
increasing the speed and efficiency of the signaling process
...
BILAYER DEFORMATION BY THE MEMBRANE PROTEINS


Cell membranes assume many different shapes, as illustrated by the elaborate
and varied structures of cell-surface protrusions and membrane-enclosed
organelles in eukaryotic cells
...




Membrane shape is controlled dynamically, as many essential cell processes
including vesicle budding, cell movement, and cell division require elaborate
transient membrane deformations
...




A crucial part in producing these deformations is played by membranebending proteins, which control local membrane curvature
...




Membrane-bending proteins attach to specific membrane regions as needed
and act by one or more of three principal mechanisms:



1
...
Increasing the area of only one leaflet causes
the membrane to bend
...




2
...
The coat proteins that shape
the budding vesicles in intracellular transport fall into this class
...
Some membrane-bending proteins cause particular membrane lipids to
cluster together, thereby inducing membrane curvature
...
For
example, the large head group of phosphoinositides make these lipid
molecules wedge-shaped, and their accumulation in a domain of one leaflet of
a bilayer therefore induces positive curvature
...


21
...




The major RBC proteins are a variety of enzymes (including glyceraldehyde 3‐
phosphate dehydrogenase, one of the enzymes of glycolysis), transport proteins
(for ions and sugars), and skeletal proteins (e
...
, spectrin)
...




Band 3, which gets its name from its position in an electrophoretic gel is present as
a dimer composed of two identical subunits (a homodimer)
...




Band 3 protein serves as a channel for the passive exchange of anions across the
membrane
...




In the lungs, where carbon dioxide is released, the reaction is reversed and
bicarbonate ions leave the erythrocyte in exchange for chloride ions
...




Glycophorin A was the first membrane protein to have its amino acid sequence
determined
...




Unlike band 3, each glycophorin A subunit spans the membrane only once, and it
contains a bushy carbohydrate cover consisting of 16 oligosaccharide chains that
together make up about 60 percent of the molecule’s weight
...




Because of these charges, red blood cells repel each other, which prevents the cells
from clumping as they circulate through the body’s tiny vessels
...




At the same time, the band 3 proteins in these individuals are more heavily
glycosylated, which apparently compensates for the otherwise missing negative
charges required to prevent cell–cell interaction
...




Consequently, individuals whose erythrocytes lack glycophorin A and B are
thought to be protected from acquiring malaria
...




The membrane skeleton can establish domains within the membrane that enclose
particular groups of membrane proteins and may greatly restrict the movement of
these proteins
...




Spectrin is a heterodimer approximately 100 nm long, consisting of an a and b
subunit that curl around one another
...




Spectrin is attached to the internal surface of the membrane by means of
noncovalent bonds to another peripheral protein, ankyrin which in turn is linked
noncovalently to the cytoplasmic domain of a band 3 molecule
...




This two‐dimensional network is constructed by linking both ends of each
spectrin filament to a cluster of proteins that include a short filament of actin and
tropomyosin, proteins typically involved in contractile activities
...




If the peripheral proteins are removed from erythrocyte ghosts, the membrane
becomes fragmented into small vesicles, indicating that the inner protein network
is required to maintain the integrity of the membrane
...




To traverse these narrow passageways, and to do so day after day, the red blood
cell must be highly deformable, durable, and capable of withstanding shearing
forces that tend to pull it apart
...




When first discovered, the membrane skeleton of the erythrocyte was thought to
be a unique structure suited to the unique shape and mechanical needs of this cell
type
...




Dystrophin, for example, is a member of the spectrin family that is found in the
membrane skeleton of muscle cells
...




The most debilitating mutations are ones that lead to a complete absence of the
protein in the cell
...




As a result, the muscle cells die and eventually are no longer replaced

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