PROTEIN FUNCTIONS
DANIEL MARVIN B. RAMEL
RENCE MARRION M. PINEDA
Some Functions/Roles of Proteins…
Gene Regulatory Protein
Enzymatic Proteins
Storage/Nutrient Proteins
Structural Proteins
Hormonal/ Signal Proteins
Receptor Proteins/ Sensory Proteins
Transport Protein
Know its role…
Protein Type Function
collagen and elastin Structural are common constituents of
extracellular
matrix and form fibers in tendons
and
ligaments
hemoglobin Transport Protein carries oxygen
a-keratin Structural Forms fibers that reinforce
epithelial cells and is the major
protein in hair and horn.
DNA polymerase Enzymes copies DNA
actin Structural forms filaments that
underlie and support the plasma
membrane
Know its role…
Protein Type Function
serum albumin Transport Protein carries lipids
tubulin Structural forms long, stiff
Microtubules
adrenergic receptor on heart Receptor Proteins increases the rate of heartbeat
muscle when it binds
to adrenaline.
Ca2+ pump Transport Protein cells pumps the calcium ions
needed to trigger muscle
contraction into the
endoplasmic reticulum, where they
are stored.
tryptophan synthetase Enzyme makes the
amino acid tryptophan
catalyzes the final two steps in the
biosynthesis of tryptophan
Know its role…
Protein Type Function
kinesin Motor Protein interacts with microtubules to
move organelles around the cell
bacteriorhodopsin Transport Protein light-activated proton pump that
transports H+
netrin Signal Proteins attracts growing nerve cells
in a specific direction in a
developing embryo;
acetylcholine receptor in the Receptor Proteins receives chemical
membrane of a muscle cell signals released from a nerve
ending;
ribulose Enzymes —helps convert
bisphosphate carboxylase carbon dioxide into sugars in
plants;
Know its role…
Protein Type Function
Casein in milk Storage Protein Found in milk and is a source of
amino
acids for baby mammals.
Myosin; Motor Protein Found in skeletal muscle cells
which provides the motive force for
humans to
move
transferrin Transport Protein carries iron
nerve growth factor (NGF) Signal Proteins stimulates some
types of nerve cells to grow axons;
insulin receptor Receptor Proteins allows a liver cell to respond
to the hormone insulin by taking up
glucose;
Know its role…
Protein Type Function
epidermal Signal Proteins stimulates the growth
growth factor (EGF) and division of epithelial cells.
Pepsin Enzymes degrades
dietary proteins in the stomach;
dynein Motor Protein enables eucaryotic cilia and flagella
to beat.
the glucose carrier Transport Protein shuttles
glucose into and out of liver cells;
ferritin; Storage Protein Binds to iron which in turn stores
the iron in the liver
Protein kinase Enzymes adds a phosphate group to a
protein molecule
Know its role…
Protein Type Function
lactose repressor in bacteria Gene Regulatory Protein silences the genes for the enzymes
that
degrade the sugar lactose
insulin Signal Proteins controls glucose levels in
the blood;
Rhodopsin in the retina Receptor Proteins detects
light
ovalbumin in egg white; Storage Protein used as a source
of amino acids for the developing
bird Embryo
homeodomain proteins Gene Regulatory Protein act as genetic
switches to control development in
multicellular organisms, including
humans.
Protein Type Function
The antifreeze proteins of protect their blood
Arctic and Antarctic fishes. against freezing
green fluorescent protein from emits a green light;
Jellyfish
monellin, a protein has an intensely sweet
found in an African plant taste;
glue proteins attach mussels and other marine
organisms firmly to rocks,
even when immersed in seawater
Question…
How do proteins carry out all of these
functions at the molecular level?
Molecular Mechanisms of Protein
Function
A protein molecule does work/ does its function when it is has physical interaction with other
molecules
Some Definitions…
Ligand – any molecule (ion, small molecule or a macromolecule that binds to a protein
Binding Site – a place in the protein where the ligand binds
Requirements for Interaction…
the ligand must fit precisely into the protein’s binding site, which results to a large
number of noncovalent bonds that form between the protein and the ligand.
These noncovalent bonds could be hydrogen bonds, electrostatic attractions, and van der
Waals attractions—plus favorable hydrophobic interactions
What happens during an interaction?
GLUCOSE
It causes a change in the
conformation/ shape of the
protein.
Causes the substrate to bind
tightly
Such change in shape brings
about a reaction that results to a
new product.
GLUCOSE-6-
https://www.youtube.com/watch PHOSPHATE + ADP
?v=Tn7HJphCBgc
Some ideas…
Binding of these ligands is specific
A protein may have also several binding sites/ active site
thus...
A protein may bind several ligands at several sites
The Binding of a Ligand Can Change the Shape of a Protein
Two Ligands That Bind to the Same Protein Often
Affect Each Other's Binding
The binding of a ligand to one site affects the affinity either positively or
negatively for the other binding sites
Positive Cooperativity
Binding of a ligand/substrate to an active site increases the affinity of another
substrate to bind in another active site
Negative Cooperativity
Binding of a ligand/substrate to an active site decreases the affinity of another
substrate to bind to another active site
Cooperative Binding
Some ideas..
Sometimes, another ligand (inhibitor) which
resembles the shape of the substrate binds to
the active site thus…
Prevents the binding of the substrate molecule
to the protein
This called COMPETITIVE INHIBITION
Penicillin, for example, is a competitive inhibitor that blocks the
active site of an enzyme that many bacteria use to construct their
cell
Some ideas…
Sometimes, an inhibitor molecule does
not bind to the active site of the
protein. Instead, it binds to another site
which is called an…
ALLOSTERIC SITE
Noncompetitive
Inhibition – an inhibitor
binds to the allosteric site
which changes the
proteins conformation
resulting to the altering
of the active site thereby
preventing the substrate
from binding.
Uncompetitive Inhibition –
an inhibitor binds to the
allosteric site created by
enzyme substrate complex.
This results to the inhibition
of the formation of a
product
Allosteric site defined
The place on an enzyme where a molecule that is not a substrate may bind, thus changing the
shape of the enzyme and influencing its ability to be active.
Allosteric Transitions Result to Regulation
of Protein Function
The shifting of a protein from
active conformation to
inactive conformation is
affected by the final product
in the series of reactions
Cooperative Allosteric Transitions:
Aspartate Transcarbamoylase (ATCase)
CTP serves as an
allosteric inhibitor for the
ATCase
The binding of allosteric
inhibitor (CTP) enhances
the affinity of other
subunits to CTP which
An allosteric enzyme that catalyzes the shifts the enzyme from
first step of pyrimidine formation Cytosine active to inactive state
triphosphate (CTP)
Another way of driving allosteric
Transitions…
Protein phosphorylation is used
so extensively that more than
one-third of the 10,000 or so
proteins in
a typical mammalian cell appear Protein Phosphorylation
to be phosphorylated at any one
time.
Protein Phosphorylation
Protein phosphorylation involves
the enzyme-catalyzed transfer of
the terminal phosphate group of
ATP to the hydroxyl group on a
serine, threonine,or tyrosine
side chain of the protein
Protein Phosphorylation Is a Common Way of
Driving Allosteric Transitions in Eucaryotic
Cells
Some applications:
the complicated series of events
that takes place as a eucaryotic cell
divides is timed in this way
many of the signals generated by
hormones and neurotransmitters
are carried from the plasma
membrane to the nucleus by a
cascade of protein phosphorylation
events
A Eucaryotic Cell Contains Many Protein
Kinases and Phosphatases
An evolutionary tree of
selected protein
kinases in eukaryotic
cells
A closer look at Cdk Protein Kinase…
ActivationSimilar to a the
of Cdk requires
following inputs:
microchip, Cdk
• binding of cyclin
Protein Kinase
• a phosphate must be added
acts
to a as a processing
specific threonine side
chain
device before
• phosphate elsewhere in the
it
protein (covalently
produces anbound to a
output
specific tyrosine side chain)
must be removed.
Cyclin binding Cyclin binding also
removes the Cyclin binding permits
allows the rapid
the addition of the
Mechanism…
distortion addition of the
inhibitory phosphate
activating phosphate
group to the tip of the
flexible loop
The kinase is finally
ATP-binding site is activated when a
distorted, and a flexible specific phosphatase
loop of about 20 amino removes the inhibiting
acids blocks access of phosphate
the protein substrate to
the active site.
GTP binding protein
Another way of driving allosteric
hydrolyzes GTP to
Instead of the phosphate
Transitions… GDP. The loss of a
being transferred
phosphate in the
nucleotide results to enzymatically from ATP to a
The binding of GTP a conformational protein, it is the phosphate
therefore activates change in the protein containing guanosine
the protein that leads to its triphosphate that binds to the
inactivation protein
GDP-bound
Other Proteins Control the Activity of GTP-binding
conformation
Proteins
encounters by Determining Whether GTP or GDP Is Bound
a guanine
nucleotide releasing
Protein is inactivated by a GTPase-
protein (GNRP), which
activating protein (or GAP), which
binds to GDP-Protein
binds to it and
assembly and causes it
induces it to hydrolyze its bound
to release its GDP.
GTP molecule to GDP
GTPase Activating Protein
GNRP activates the protein by (GAP)
indirectly adding back the Guanine nucleotide
phosphate Releasing Protein (GNRP)
removed by GTP hydrolysis
RAS Protein: Example of a GTP Binding
Protein
The regions shown in blue
change their conformation when
the GTP molecule is hydrolyzed
to GDP and inorganic phosphate
by the protein; the GDP remains
bound to the protein, while the
inorganic phosphate is released.
This shows how the loss of a single phosphate group,
Effect of GTP Binding and Hydrolysis on a
which initially causes only a tiny movement of 0.1
Multi-subunit protein: Ef-tu protein nm or so at the binding site, is magnified by the
protein to create a movement 50 times larger
Allosteric transition triggered by the gain or loss
of a phosphate on the bound guanine nucleotide
can cause a major shape change in a GTP binding
protein
Proteins That Hydrolyze ATP Do Mechanical Work
in Cells
Conformational changes enable
proteins whose major function is to
move other molecules, the motor
proteins, to generate the forces
responsible for muscle contraction
and many of the dramatic
movements of cells.
Motor protein video
ATP-driven Membrane-bound Allosteric Proteins Can Act as Ion
Pumps
An important example is the Na+-
K found in the plasma membrane
of all animal cells, which pumps 3
Na+ out of the cell and 2 K+ in
during each cycle of
conformational changes driven by
ATP hydrolysis
ATP-driven Membrane-bound Allosteric Proteins Work in
Reverse to Synthesize ATP
The membrane-bound allosteric pumps
that are driven by ATP hydrolysis can also
work in reverse and employ the energy in
the ion gradient to synthesize ATP.
Here, the energy available in the H+
gradient across the inner mitochondrial
membrane is used in this way by the
membrane-bound allosteric protein
complex, ATP synthase, which synthesizes
most of the ATP required by animal cells.
Energy-coupled Allosteric Transitions in Proteins Allow the Proteins to
Function as Motors, Clocks, Assembly Factors, or Transducers of
Information
Proteins Often Form Large Complexes
That Function as Protein Machines
