STRUKTUR DAN

FUNGSI
PROTEIN

Joko Marwoto
To a large extent cells are made of
proteins.

Protein determine the shape and

structure of the cell and also serve as
instruments of molecular recognition
and catalysis.
In computer terminology, the nucleic
acids represent the “software” –
instructions
that a cell receives from its parent.

Proteins make up the “hardware”- the

physical apparatus that executes the
program stored in the memory.
DNA and RNA consist of a series of
nucleotides, all being chemically very
similar to one another, assembled into
giant molecules having much the same
chemistry whatever their sequence.
PROTEIN are made from an
assortment of 20 very different amino
acids, each with a distinct chemical
personality.

This variety allows for enormous

versatility in the chemical properties of
different proteins.
The shape of a Protein Molecule Is
Determined by Its Amino Acid
Sequence
Many of the bonds in a long
polypeptide chain allow free
rotation of the atoms they join,
giving the protein backbone
great flexibility.
In principle then, any protein molecule
can adopt an enormous number
different shapes, or conformation of a
protein unusual stability.
The folding of protein into a globular
conformation
The polar amino acid side chains
tend to be exposed on the outside
of the protein; the nonpolar amino
acid side chains are buried on the
inside to form a hydrophocic core “
hidden” from the water.
Common Folding Patterns Recur in
Different Protein Chains

More than 200 proteins have been

completely analyzed by x-ray diffraction
analysis.

Each of these proteins has a specific

conformation.
The structure of the beta-sheet makes up
extensive regions of the core of most
(though not all) globular proteins.

The three dimensional conformation of the

protein egg-white lysozyme as seen in four
commonly used representations.
An alfa-helix is generated when a single
polypeptide chain turns regularly about
itself to make a rigid cylinder in which each
peptide bond is regularly hydrogen-
bounded to other peptide bonds
elsewhere in the chain.
Alfa-helix
Proteins Are Enormously
Versatile in Structure

The variety of their amino acid side

chains, proteins arare remarkably
versatile with respect to the type of
structures they can form.
Proteins Are Enormously
Versatile in Structure

Once extreme case is the family of

collagen molecules found in the
extracelluler space.

At the other extreme is the extracellular

protein elastin
(like rubber)
Proteins Show Different Levels
of Structural Organization

Though the number of different ways

in which even a small protein could
fold up is astronomically large, there
seems to be some logic in the way in
which it occurs.
Proteins Show Different Levels
of Structural Organization

The three-dimensional structure of a

protein can be described in terms of
four different levels of folding, each
of which is constructed from the
preceding one in hierarchical
fashion.
Alternate
nomenclature;
primary
structure,
secondary,
tertiary, dan
quarternary
structure.
Relatively Few of the Many Possible
Polypeptide Chains Would Be Useful

Since each of the 20 amino acids is

chemically distinct and each can, in
principle, occur at any position in a
protein chain, there are
20 X 20 X 20 20 = 160,000 different
possible polypeptide chains n amino
acids long.
Relatively Few of the Many Possible
Polypeptide Chains Would Be Useful

For a typical protein length of about

300 amino acids , more than 10 390
different proteins can be made.
New Proteins Often Evolve by
Minor Alterations of Old Ones
Cells have genetic mechanisms
that allow genes to be duplicated
and modified in the course of
evolution.
New Proteins Often Evolve by
Minor Alterations of Old Ones
Example; family of protein-
cleaving (proteolytic) enzymes
called serine proteases.
Myoglobyn (blue), heamin (orange)

• ligand
New Proteins Often Evolve Through
the Combination of Different
Polypeptide Domains

Once a number of stable protein

surfaces have been made in a cell,
new surfaces with different binding
properties can be generated by the
joining of two or more individual
proteins together by noncovalent
interactions between them.
New Proteins Often Evolve Through
the Combination of Different
Polypeptide Domains

Juxtaposition of separate protein

surfaces, in the course of
evolution, could give rise to new
binding sites for small moleculess
called ligands.
Protein subunits Can Self-
assemble into Large Structures
in the Cell
The same principles that enable
several protein domains to
associate to form binding sites
operate to generate much larger
structures in the cell.
A Single Type of Protein subunit Can
Interact with Itself to form
Geometrically Regular Aggregates

If a protein has a binding site that is

complemntary to a region of its
own surface, it will assemble
spntaneously into an aggregate
structure.
Exp: symmetrical dimmer
A Single Type of Protein subunit Can
Interact with Itself to form
Geometrically Regular Aggregates

An example of a helical structure

commonly encountered in cells is
ten actin filament, which has two
helical strands wound around each
other and is formed from a single
globular protein subunit called
actin.
Self-assembling Aggregates Can
Include Different Protein Subunits
and Nucleic Acids

Many carge cellular structures

are constructed from a mixture
of different proteins.
In some cases, such as viruses
and ribosomes, RNA, DNA.
There Are Limits to Self-assembly

It is logical to ask whether all

cellular structures that are held
together by noncovalent bonds
are capable of self –assembly.
There Are Limits to Self-assembly

Can a mitochondrion, a cilium, a

myofibril, or even a whole cell
form spontaneously out of a
solution of their component
macromolecules?
There Are Limits to Self-assembly
No, because for large and
complex structures part of the
information for assembly is
provided by special enzymes and
by other cellular proteins that
perform the function of jigs or
template.
The three-dimensional conformation a
protein molecule is determined by its amino
acid sequence.

Particular folded structures are stabilized by

nonco alent interactions between different
parts of the polypeptide chain.

Small globular regions known as domains are

the modular units from which many proteins
are constructed;
Proteins are brought together into
aggregates structure by the same forces that
determine protein folding.

Proteins with binding sites for their own

surface can assemble into dimers or larger
oligomers, closed rings, spherical shells, or
helical polymers.
Mixtures of many different proteins, which
can also include structural nucleic acids, can
spontaneously assemble into large complex
structures in the test tube.

However, in many assembly processes

irreversible steps occur so that not all
structures in the cell are capable of
spontaneous reassembly if they are
dissociated into their component parts.
 PROTEIN FUNCTION

The chemical properties of a protein

molecule depend almost entirely on
its exposed residues, which are able
to form different types of weak
noncovalent bonds with other
molecules.
 PROTEIN FUNCTION
An effective interaction of a protein
molecule with anther molecule (referred
to as a ligand) requires that a number of
weal bods be formed simultaneously
between them.

Therefore, the only ligands that can bind

tghtly to a protein are those that fit
precisely onto its surface.
 PROTEIN FUNCTION

The region of a protein that

associates with a ligand, known as its
binding site, usually takes the form
of a cavity formed by a specific
arrangement of amino acids on the
protein surface.
A Protein’s Conformation Determines
Its Chemistry

Neighboring surface residues on a

protein often interact in a way that
alters the chemical reactivity of
selected amino aced side chains.
A Protein’s Conformation Determines
Its Chemistry

First, neighboring parts of the

polypeptide chain may interact in a way
that restricts the access of water
molecules to other parts of the protein
surface.
A Protein’s Conformation Determines
Its Chemistry
Second, the clustering of neighboring
polar amino acid side chains alters their
reactivity.
For exp: a number of negatively charged
side groups can be forced together
against their mutual repulsion by the way
that the protein folds.
Substrate Binding Is the First Step in
Enzyme Catalysis
One of the most important functions of
proteins is to act as enzymes that
catalyze specific chemical reactions.
The ligand in this case is the substrate
molecule, and the binding of the
substrate to the enzyme is an essential
prelude to the chemical reaction.
Substrate Binding Is the First Step in
Enzyme Catalysis

The way enzymes work;

If the concentration of substrate is
increase, the rate at which product is
formed also increases up to a max. value.
This rate is expressed as a turnover
number.
Enzymes Accelerate Reaction Rates
Without Shifting Equilibria

No matter how sophisticated an enzyme

becomes, it cannot make the chemical
reaction that it catalyzes either more or
less energetically favorable.
Many Enzymes Make Reactions Proceed
Preferentially in One Direction by Coupling
Them to ATP Hydrolysis.
The product of each enzyme usually
serves as a substrate for another enzyme
in the metabolic pathway and is rapidly
consumed.
Many reactions are driven by being
coupled to the hydrolysis of ATP to ADP
and inorganic phosphate.
Multienzyme Complexes Help to
Increase the Rate of Cell metabolism.

Both the efficiency of enzymes in

accelerating metabolic reactions and
their organization in the cell are crucial to
the maintenance of life.
Intracellular Membranes Increase the
Rates of Diffusion-limited Reactions.

The extensive intracellular membranes of

eucaryotic cells act in at least two distinct
ways to increase the rates of reaction
that would otherwise be limited by the
speed diffusion.
Intracellular Membranes Increase the
Rates of Diffusion-limited Reactions.

First, .membranes can segregate certain

substrates and all the enzyme that act on
them into the same membrane-limited
compartment, as in the mitochondrion or
the cell nucleus.
Intracellular Membranes Increase the
Rates of Diffusion-limited Reactions.
Second, membranes can restrict the
diffusion of reactants to the two
dimensions of the membrane itself so
that enzymes and their substrates are
much more likely to collide with each
other than if they were diffusing in three
dimensions.
Protein Molecules Can Reversibly
Change Their Shape

Because the mechanics of cellular life

generally demand stable molecular
structure, evolutionary pressures have
worked against the ability of
polypeptides to change randomly from
one conformation to another.
Protein Molecules Can Reversibly
Change Their Shape

Protein with this property are known as

allosteric proteins.
Each distinct conformation of an
allosteric protein has a somewhat
different surface and thus a different
ability to interact with other molecules.
Allosteric Protein Are Involved in
Metabolic Regulation

Allosteric protein are essential to the

feedback regulation that control the flux
through a metabolic pathway.
Enzyme, that act early in a pathway are
almost always allosteric proteins that
can exist in two different conformations.
Allosteric Protein Are Vital for Cell
Signaling

Allosteric protein such as those involved

in feedback regulation have at least two
binding sites, one for the enzyme
substrate and one or more for regulatory
ligands.
Protein Can Be Pushed or Pulled into
Different Shape

All of the directed movements in cells

depend on forces generated by proteins.
Consider an allosteric protein that can
adopt two alternative conformations;
a low energy form C (inactive) and
a high-energy form C* (active)
Protein Can Be Pushed or Pulled into
Different Shape

An input of chemical energy can be used

to “push” conformation C to the active
form C* in much less reversible manner.
Common: a phosphate group from ATP to
a serine, threonine, or tyrosine residue in
the protein, forming a covalent linkage.
Energy-driven Changes in Protein
Conformations Can Do Useful Work

Suppose a protein is required to “walk” a

long a narrow thread, such as a
microtubule or a DNA molecule.
DNA helicase, a protein that plays an
essential part in DNA replication
ATP-driven Membrane-bound
Allosteric Proteins Can Act as Pumps

Allosteric proteins can use the energy of

ATP hydrolysis to do other forms of work,
such as pumping specific ions into or out
of the cell.
Na, K , ATPase
Protein Molecules Can Harness Ion
Gradients to Do Useful Work
The large Na gradient across the plasma
membrane generated by the Na, K,
ATPase is used to drive other plasma-
membrane-bound protein pumps that
transport glucose or amino acids into the
cell.
“ping-pong” pump oscilates
 Summary
• The biological function of a protein depends on
the detailed chemical properties of its surface.
• Binding sites are formed as surface cavities in
which precisely positioned amino acid chains are
brought together by protein folding.
• Enzymes catalyze chemical changes in bound
substrate molecules, often employing small,
tightly bound coenzyme molecules to extend the
range of their reactions.
 Summary
• Allosteric proteins reversibly change their
shape when ligands bind to their surface.
• The changes produced by one ligand can
affect the binding of a second ligand, thereby
providing a mechanism for regulating various
cell processes.
• Such changes in protein shape are often
driven in an unidirectional manner by the
expenditure of chemical energy.