Protein classification.

Protein misfolding.

Sopio Dzneladze
 Protein classification.
• Simple Proteins.
This category includes proteins that, when
broken down by hydrolysis give only amino
acids;
• Albumin.
Ovalbumin – from egg;
Lactalbumin – from milk;
Serum albumin – from plasma serum;
Legumelin – from plants.
Sopio Dzneladze
 Simple Proteins.

• Globulins;
• Histones;
• Protamines;
• Glutelin an gliadin;
• Scleroproteins or albuminoids: keratin,
collagen and elastin.

Sopio Dzneladze
 Conjugated Proteins.

This category includes proteins that are

associated with other compounds.
The protein moiety is commonly called
apoprotein, while the other component is
known as prosthetic group.

Sopio Dzneladze
Sopio Dzneladze
•Chromosomes are proteins conjugated with RNA;
•Ribosomes are proteins conjugated with DNA;

Sopio Dzneladze
 Chromoproteins
Protein associated with a color prosthetic group:
hemoglobin, cytochromes, flavoproteins
(involved in redox processes), and rhodopsin
(present in retina, plays an important role in
the process of vision).

Sopio Dzneladze
 phosphoproteins
• A phosphoprotein is a protein that is
posttranslationally modified by the
attachment of either a single phosphate
group, or a complex molecule such as 5'-
phospho-DNA, through a phosphate group.
The target amino acid is most often serine,
threonine, or tyrosine residues, or aspartic
acid or histidine residues.

Sopio Dzneladze
A glycoproteins are class of proteins which have
carbohydrate groups attached to the
polypeptide chain.
A lipoproteins are type of proteins where
prosthetic group is represented by various
kinds of lipids.

Sopio Dzneladze
Sopio Dzneladze
• A metalloproteins are group of proteins that
are conjugated with metals, such as Fe, Cu, Zn,
Mg, Mn, which are essential for the structure
and function of those molecules.
• Fe containing: hemoglobin, myoglobin,
cytochromes;
• Cu containing: ceruloplasmin, cytochrome
oxidase;
• Mg containing: kinases and phosphatases;
• Zn containing: insulin and carbonic anhydrase

Sopio Dzneladze
 Protein folding
• Interactions between the side chains of amino
acids determine how a long polypeptide chain
folds into the intricate three-dimensional
shape of the functional protein.
• As a peptide folds, its amino acid side chains
attracted and repulsed according to their
chemical properties.

Sopio Dzneladze
 Chaperones
• The information needed for correct protein
folding is contained in the primary structure of
the polypeptide;
• Specialized group of proteins – chaperones –
are required for the proper folding of many
species of proteins.
• Chaperones interact with a polypeptide at
various stages during the folding process.

Sopio Dzneladze
• Some chaperones are important in keeping the
protein unfolded until its synthesis is finished or act
as catalysts by increasing the rate of the final stages
in the folding process.
• Others protect proteins as they fold so that their
vulnerable, exposed regions do not become tangled
in unproductive interactions.

Sopio Dzneladze
 Protein misfolding.
• Protein folding is a complex, trial-and-error
process that can sometimes result in improperly
folded molecules.
• Misfolded proteins are usually tagged and
degraded within the cell.
• Intracellular or extracellular aggregates of
misfolded proteins can acumulate, particularly as
individuals age.
• Deposits of these misfolded proteins are
associated with number of diseases.
Sopio Dzneladze
Sopio Dzneladze
 Amyloid disease
• Misfolding of proteins can occur spontaneously, or be
caused by mutation in a particular gene, which then
produces an altered protein;
• Some normal proteins can take on a unique
conformational state, that leads to the formation of
long, fibrilar protein assemblies consisting of β-pleated
sheets;
• Accumulation of these insoluble, spontaneously
aggregating proteins –amyloids – has been implicated
in many degenerative diseases.
Sopio Dzneladze
Sopio Dzneladze
 Alzheimer’s disease is an irreversible,
progressive brain disorder that slowly destroys
memory and thinking skills, and, eventually,
the ability to carry out the simplest tasks.
Alzheimer’s disease is currently
ranked as the sixth leading cause
of death in the United States, but 
recent estimates indicate that the
disorder may rank third, just
behind heart disease and cancer,
as a cause of death for older
people.

Sopio Dzneladze
 Alzheimer’s is the most common cause of dementia
among older adults.
 Dementia is the loss of
cognitive functioning—
thinking, remembering,
and reasoning—and
behavioral abilities to
such an extent that it
interferes with a
person’s daily life and
activities.

Sopio Dzneladze
• Alzheimer’s disease is named after Dr. Alois Alzheimer.
In 1906, Dr. Alzheimer noticed changes in the brain
tissue of a woman who had died of an unusual mental
illness. Her symptoms included memory loss, language
problems, and unpredictable behavior.

•After she died, he

examined her brain and
found many abnormal
clumps (now called
amyloid plaques) and
tangled bundles of fibers
(now called
neurofibrillary, or tau,
tangles). Sopio Dzneladze
• Another feature is the loss of connections
between nerve cells (neurons) in the brain.
Neurons transmit messages between different
parts of the brain, and from the brain to
muscles and organs in the body.

Sopio Dzneladze
• The damage initially appears to take place in
the hippocampus and the entorhinal cortex,
parts of the brain essential in forming
memories. As more neurons die, additional
parts of the brain are affected and begin to
shrink. By the final stage of Alzheimer’s,
damage is widespread, and brain tissue has
shrunk significantly.

Sopio Dzneladze
 Mild Alzheimer’s Disease
• As Alzheimer’s disease progresses, people
experience greater memory loss and other
cognitive difficulties. Problems can include 
wandering and getting lost, trouble 
handling money and paying bills, repeating
questions, taking longer to complete normal
daily tasks, and 
personality and behavior changes. People are
often diagnosed in this stage.

Sopio Dzneladze
 Moderate Alzheimer’s Disease
• In this stage, damage occurs in areas of the brain
that control language, reasoning, sensory
processing, and conscious thought. Memory loss
and confusion grow worse, and people begin to
have problems recognizing family and friends.
They may be unable to learn new things, carry out
multistep tasks such as getting dressed, or cope
with new situations. In addition, people at this
stage may have 
hallucinations, delusions, and paranoia and may
behave impulsively.
Sopio Dzneladze
 Severe Alzheimer’s Disease

• Ultimately, plaques and tangles spread

throughout the brain, and brain tissue shrinks
significantly. People with severe Alzheimer’s
cannot communicate and are completely
dependent on others for their care. 
Near the end, the person may be in bed most
or all of the time as the body shuts down.

Sopio Dzneladze
 Biochemistry of disease
• The dominant component of the amyloid
plaque that accumulates in Alzheimer disease
is amyloid β (Aβ) – a peptide containing 40-42
amino acid residues.
• This peptide when aggregated in a β-plated
sheet configuration – is neurotoxic, and is
central pathogenic event leading to the
cognitive impairment characteristic of the
disease.
Sopio Dzneladze
Sopio Dzneladze
• A second biologic factor involved in the
development of Alzheimer disease is an
accumulation of neurofibrillary tangles inside
neurons.

• Component of these tangled fibers is an

abnormal form of the tau protein, which in its
healthy version helps in an assembly of the
microtubular structure.

Sopio Dzneladze
Sopio Dzneladze
Normal and dying neuron in Alzheimer
disease

Sopio Dzneladze
Sopio Dzneladze
 Prion disease
• Prion diseases occur when
normal prion protein, found on the surface of
many cells, becomes abnormal and clump in
the brain, causing brain damage. This
abnormal accumulation of protein in the brain
can cause memory impairment, personality
changes, and difficulties with movement.

Sopio Dzneladze
• The prion protein (PrP) has been strongly
implicated as the causative agent of transmissible
spongiform encephalopathies (brain disease,
damage, or malfunction) – TSEs, including:
• Creutzfeld-Jakob disease in humans;
• scarpie in sheep;
• and bovine spongiform encephalopathy in cattle
(mad cow disease);
• The TSEs are invariably fatal, and no treatment is
currently available that can alter this outcome.

Sopio Dzneladze
 Creutzfeldt – Jacob Disease
• CJD is caused by a protein known as a prion.
Infectious prions are misfolded proteins that can
cause normally folded proteins to become
misfolded. Most cases occur spontaneously, while
about 7.5% of cases are 
inherited from a person's parents in an autosomal
dominant manner. Exposure to brain or spinal
tissue from an infected person may also result in
spread. There is no evidence that it can spread
between people via normal contact or 
blood transfusions.
Sopio Dzneladze
Sopio Dzneladze
 Sheep Scarpie
• Infectious protein PrP scarpie;
• Noninfection form PrP cellular, encoded by the
same gene as an infectious agent, presented
in neurons and glial celss.
• No primary structure differences or alternate
posttranslational modifications have been
found between normal and infection forms.

Sopio Dzneladze
• The key to becoming infectious apparently lies
in changes in the three-dimentional
conformation of PrPc: number of α-helices
present in noninfectious are replaced by β-
sheets in the infectious form.

Sopio Dzneladze
• Interaction of the infectious
PrP molecule with a normal
PrPcauses the normal form to
fold into the infectious form;

• these two molecules

dissosiate and convert two
additional noninfectious PrP
molecule to the infectious
form;

• this results in an increase of

an infectious form.
Sopio Dzneladze
Sopio Dzneladze
 PP:21-22
Lippincott's Illustrated Reviews Biochemistry, 6E
Question of the Diseases

Sopio Dzneladze