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STRUCTURE
ROLE IN HUMAN
DISORDERS
COURTNEY S. ZAHN
IMPORTANCE OF PROTEINS
Proteins are macromolecules involved in every aspect of all
living things.
Without proteins, Biology as we know it would not exist.
Proteins are the most versatile macromolecules.
Proteins constitute over 50% of dry weight of cells.
COMPOSITION OF PROTEINS
AMINO ACIDS
-
AMINO ACIDS
- Peptide bonds are a special covalent bond which link
amino acids together in proteins to form a polypeptide
chain.
- Some proteins are a single polypeptide chain, and
others consist of multiple chains held together by weak
bonds.
- Formation of proteins is rapid.
- Polypeptide chains are formed and folded into their
correct shapes in a matter of seconds.
DENATURING OF PROTEINS
Conditions which can cause proteins to denature:
High Temperatures
Alkalosis
Acidosis
Osmotic Shock
Oxidative Stress
DENATURING OF PROTEINS
These environmental stressors break down proteins,
changing their structures, and re-directing their fate.
The result is a NONFUNCTIONING protein.
Sometimes denaturation is reversible (chemical denaturing
agent removal). In these cases, the protein can
spontaneously refold into its original functional state.
CHAPERONES
-
Usually, proteins fold into their most stable state spontaneously and
correctly.
- Alzheimers disease
- Cystic fibrosis
- Parkinsons disease
- Huntingtons disease
- CreutzfeldtJakob disease
- Gauchers disease
- and many other degenerative and neurodegenerative
disorders
PROTEIN AGGREGATES
Structural changes in proteins can lead to masses of aggregates,
which sometimes result in neurotoxicity and the death of cells.
Misfolded/aggregated proteins called prions become neurotoxic
and are also involved in human disorders or diseases.
Transmissible spongiform encephalopathies (TSEs) are fatal brain
diseases, which are associated with misfolded proteins.
TSEs are thought to be the result of prions causing other similar
proteins to change shape as well.
Mad cow disease is an example of a TSE.
Many p53-mediated cancers are also the result of protein
misfolding.
Mutations in proteins that function as major regulators of growth
and differentiation may cause cancers and other proteinmisfolding disorders.
AMYLOIDS
Frequently, protein misfolding can cause the formation of a harmful
amyloid.
Amyloids are formed when aggregates of proteins are transformed into
a great number of highly insoluble hydrogen bonds within a fibrillar
structure.
Plaque-like structures form from the accumulation of these amyloids.
This gain of function is another devastating effect of improper folding
of a proteins structure, and can be observed in Alzheimer disease,
Parkinsons disease and Huntingtons disease.
These amyloid-related neurodegenerative diseases are often
accompanied by the appearance of a toxic function
AMYLOIDS
CONCLUSION
Hopefully, research will continue and eventually
we will be able to completely understand the
role of protein structure in human disorders.
For now, just knowing that it is important, is a
great starting point for future research. A small
error in the improper folding of proteins can be
lethal. Down the road, it would be incredible to
see chaperone protein therapy for
neurodegenerative disorders and the like.