5. Carrier Proteins
They do not extend through the membrane. They bond and drag
molecules through the lipid layer and release them on the opposite side.
9. LIGANDS:
• They are extra cellular signaling molecules that
bind to cell surface receptors & trigger events
inside the cell.
SIGNAL TRANSDUCTION:
• Any process by which cell converts one kind of
signal or stimulus into other.
10. AMPLIFIER PROTEINS:
• They are usually either enzymes or ion channels.
• Amplifiers increase the received signals by
producing large amounts of small intracellular
signaling proteins.
RELAY PROTEINS:
• They pass the message to the next signaling
component in the chain without otherwise
participating.
11. In biochemistry, a receptor is a molecule found on
the surface of a cell, which receives specific
chemical signals from neighbouring cells or the
wider environment within an organism.
These signals tell a cell to do something—for
example to divide or die, or to allow certain
molecules to enter or exit the cell.
Receptors are protein molecules, embedded in either
the plasma membrane (cell surface receptors) or
the cytoplasm (nuclear receptors) of a cell, to which
one or more specific kinds ofsignaling molecules
may attach
12. A molecule which binds (attaches) to a receptor is
called a ligand , and may be a peptide (short protein)
or other small molecule, such as a neurotransmitter,
a hormone, a pharmaceutical drug, or a toxin
Each kind of receptor can bind only certain ligand
shapes.
Each cell typically has many receptors, of many
different kinds. Simply put, a receptor functions as a
keyhole that opens a biochemical pathway when the
proper ligand is inserted.
Ligand binding stabilizes a certain
receptor conformation (the three-dimensional shape
of the receptor protein, with no change in sequence).
13. Ligand-induced changes in receptors result in
cellular changes which constitute the biological
activity of the ligands.
14.
15.
16.
17. Na+/K+-ATPase (Na+/K+-pump)
1 ATP used for exporting 3 Na+ ions and importing 2 K+ ions.
Crucial for maintaining resting membrane potential.
18. Transporters
ATP-independent systems (However, Na+ gradient drives these transporters;
ATP-driven Na+/K+-pump generates the gradient.)
• GLUCOSE TRANSPORTER:
28. G proteins, short for
guanine nucleotide
binding proteins.
They communicate
signals from many
hormones,
neurotransmitters, and
other signaling factors.
Heterotrimeric G
proteins, composed of
alpha, beta, and gamma
subunits, are found at
the cytoplasmic surface
of the plasma membrane
and are activated by G
protein-coupled
receptors.
G Proteins
29. Receptor-activated G proteins
Receptor activated G proteins are bound to the inside surface of the cell
membrane and they consist of the α and the tightly associated βγ subunits.
When a ligand activates the G protein-coupled receptor, it induces a
conformation change in the receptor that allows the G protein to now bind to the
receptor.
The G protein then releases its bound GDP from the α subunit and binds a new
molecule of GTP.
This exchange triggers the dissociation of the α subunit, the βγ dimer, and the
receptor.
Both, α-GTP and βγ, can then activate different signaling cascades (or second
messenger pathways) and effector proteins, while the receptor is able to activate
the next G protein.
The α subunit will eventually hydrolyze the attached GTP to GDP by its
inherent enzymatic activity, allowing it to reassociate with βγ and starting a new
cycle.
A well characterized example of a G protein-triggered signaling cascade is the
cAMP pathway.
– The enzyme adenylate cyclase is activated by Gαs-GTP and synthesizes the second
messenger cyclic adenosine monophosphate (cAMP) from ATP.
Second messengers then interact with other proteins downstream to cause a
change in cell behavior.
30. G-protein activation
When not activated, the alpha subunit
binds GDP.
When the ligand binds to the GPCR it
changes conformation and, in turn, alters
the conformation of the G protein.
Altering the conformation of the alpha
subunit allows it to exchange GDP for
GTP.
The binding of GTP to the alpha subunit
causes it to dissociate from the beta
subunit.
These are now two independent entities:
the alpha subunit and the beta-gamma (bg)
subunit.
GTP binding and dissociation of the bg
subunit causes the alpha subunit to adopt a
new conformation. The alpha subunit can
now bind to intracellular signaling
proteins.
The bg subunit does not change
conformation, but its dissociation from the
alpha exposes this face of the beta subunit.
It now can also interact with signaling
molecules.
31. Inactivation of G proteins
The active alpha subunit binds to its target
protein and activates it. Common targets of
alpha subunits are enzymes and ion channels.
The internal GTPase activity of the alpha
subunit cleaves the GTP to GDP.
This conversion to GDP inactivates the alpha
subunit, causing it to dissociate from its target
protein.
The inactive alpha subunit can then associate
again with the bg subunit, reforming the
inactive G protein.
**G proteins are usually active for very short
periods of time (seconds).
**Alpha subunits have intrinsically weak
GTPase activity, and on their own would take
minutes to hydrolyze their GTP.
**GTPase activating proteins (GAPs), when
bound to the alpha subunit, enhance the GTPase
activity tremendously. GAPs are critical
negative regulators of G proteins.
**Regulator of G protein signaling (RGS)
proteins are a large family of GAPs that are
thought to be required for turning off G protein
cascades in ALL eukaryotes.
**Each RGS protein has preferred alphas that
they regulate.
33. In cell biology, Protein kinase A (PKA)
refers to a family of enzymes whose
activity is dependent on cellular levels
of cyclic AMP (cAMP).
PKA is also known as cAMP-dependent
protein kinase
Protein kinase A has several functions in
the cell, including regulation
of glycogen, sugar, and lipid metabolism.
35. cAMP
• It effects on gene transcription.
PROTEIN KINASE A
• It is heterotrimeric molecule.
36. Beta-gamma complex
– The β and γ subunits are closely bound to one another.
– The βγ complex is released from the α subunit after its
GDP-GTP exchange.
– The free βγ complex can act as a signaling molecule
itself - activating other second messengers or gating
ion channels.
37. Cholera: G Proteins are at full speed ahead
Cholera is caused by a comma-shaped bacterium, Vibrio
cholerae, which is ingested in contaminated water and
food. The bacteria multiply enormously in the intestine,
where epithelial cells allow fluid to leak into the intestine
with intense diarrhoea as a result. Cholera is endemic in
India and other parts of the third world.
The cholera bacterium is shaped like a comma
with a tail (above).
38. Cholera Toxin
cholera toxin
enzyme that catalyzes the transfer of ADP ribose
from intracellular NAD+ to alpha s.
The ADP ribosylation alters the alpha s so that it
can no longer hydrolyze its bound GTP. Thus,
alpha s continues to stimulate adenylyl cyclase to
produce cAMP.
The prolonged production of cAMP in the
intestinal epithelial cells causes a large efflux of
Na+ and water into the gut, and is responsible for
the severe diarrhea that is characteristic of cholera.
39. The bacterium can be killed by antibiotics, but
the disease is caused by a bacterial toxin, which
irreversibly activates the G proteins of epithelial
cells in the intestine. This results in an often life-
threatening loss of water and salts.
MECHANISM OF ACTION
Step 1.
Step 2.
Step3.
Step4.
40. Step 1.
The bacterium produces a toxin that is the cause of the cholera. The
toxin molecule is composed of several parts, one of which (coloured
blue) penetrates the cell membrane (yellow)
Step 2.
The toxin acts as an enzyme that changes the G protein so that it can no
longer switch itself off.
41. Step 3.
The activated G protein changes the function
of epithelial cells in the intestine, with enormous
loss of water as a result.
Cholera affects the intestine because this is the
place which the toxin reaches.
Step 4.
Intestinal villi, the minute projections
from the mucous membrane of the small
intestine, which are primarily affected by
the toxin.
42. Signs and symptoms
The primary symptoms of cholera are profuse
painless diarrhea and vomiting of clear fluid. These
symptoms usually start suddenly, one to five days after
ingestion of the bacteria.
If the severe diarrhea and vomiting are not aggressively
treated it can, within hours, result in dehydration and
electrolyte imbalances.The typical symptoms of dehydration
include low blood pressure, poor skin turgor (wrinkled
hands), sunken eyes, and a rapid pulse .
43. INSULIN RECEPTOR
• The insulin receptor is a dimeric tyrosine kinase embedded
in the plasma membrane.
• Two alpha subunits-extracellular, have insulin binding domains.
• Two beta subunits linked by disulfide bonds-within and on
cytosolic side of membrane.
44. •
• Binding of insulin to the alpha subunits causes the beta
subunits to phosphorylate themselves (autophosphorylation),
thus activating the catalytic activity of the receptor.
45. IMPORTANCE OF INSULIN RECEPTOR
Activation of the insulin receptor will lead to
the activation of the phosphatidylinositol-3
kinase (PI-3K) pathway.
This pathway will activate protein kinase B
(PKB).
Protein kinase B causes movement of the
GLUT4 glucose transporter from intracellular
membranes to the cell surface.
The influx of glucose will lower blood glucose
levels.
When blood glucose levels return to normal, the
GLUT4 transporters will be taken back into the
cell by endocytosis.
46.
47. Receptor Proteins
These proteins are used in intercellular communication. In this
animation you can see the a hormone binding to the receptor. This
causes the receptor protein release a signal to perform some action.
48. EXAMPLES:
Some surface receptors recognize ligand of low molecular
weight & other recognize macromolecules.
Blood proteins (Mr > 20,000) that carry lipids are
recognised by specific cell surface receptors and then
transported into the cell.
Antigens (proteins,virus or bacteria are recognized by
immune system as foreign bodies) bind to specific
receptors & trigger the production of antibodies.
