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PROTEINS
 What are Proteins?
 Protein Structure
 Protein Function
 Diseases Associated with Proteins
OUTLINE
WHAT ARE PROTEINS?
We are exposed to proteins
every day of our life.
Part of many foods, along with
sugar, and fat.
Meat, milk, cheese, eggs are all
rich in protein.
When we ingest protein we break
it down into it’s component parts.
These parts are used to make
proteins we need and want.
WHAT ARE PROTEINS?
 Machinery of the cell.
 Vast array of functions:
◦ Oxygen Transport
◦ Metabolism
◦ Defence
◦ Cell Signalling
 Two main types:
◦ Structural & Globular
 Made of amino acids.
PROTEIN STRUCTURE
REVIEW
AMINO ACIDS
 Proteins are made of small
compounds called amino acids.
 There are only twenty different
amino acid molecules.
 Each amino acid is similar in
size and composition, but each
of them unique.
 Amino acids combine to form
dipeptides, and polypeptides.
 Polypeptides are proteins.
PHENYLALANINE
TYROSINE
ISOLEUCINE
AMINO ACIDS
4 LEVELS OF STRUCTURE
 A protein molecule has
four levels of structure.
 Primary  Quaternary.
 1° – Amino Acid
Sequence
 2° – Small Local
Structure
 3°–Assembly of 2°
Structure
 4°–Assembly of 3°
Structure
 Two main types of
secondary structure
called:
◦ Alpha-helix
◦ Beta-sheet
PRIMARY STRUCTURE
 Amino acids combine to form a
polypeptide.
 First step in making protein a
protein molecule.
 Polypeptides can be as short as
10-20 amino acids, or as long
as 1,000 amino acids.
 Large amount of variety
available in terms of which
amino acids are used.
 DNA determines which amino
acids are used.
SECONDARY STRCUTURE
 Primary structure of amino acids
folds on top of itself to form the
secondary structure.
 Two main types of secondary
structure:
 Alpha-helix – hollow tube
 Beta-sheet - Flat panel
 These structures provides from
shape and stability to a protein
molecule.
 Silk, obtained from larvae of some
insects, 5X stronger than steel of
the same thickness.
BETA SHEET
TERTIARY STRCUTURE
 Alpha helices and beta-sheet
structures combine.
 Within the same protein
molecule you can have both
helices and sheets.
 Regions of sheet and helix are
joined together by flexible
regions of linking amino acids.
 Proteins are therefore strong
but flexible.
QUATERNARY STRUCTURE
 Some proteins are composed
of multiple subunits.
 The subunits are identical, and
combine to allow the protein to
do it’s job.
 Allows an extra level of
regulation in the protein
function.
 Example, Hemoglobin protein
for transporting oxygen.
PROTEIN FUNCTION
PROTEIN FUNCTIONS
 Vast array of proteins
performing a vast array of
functions.
 Involved in:
◦ Immune system
◦ Oxygen Transport
◦ Eyesight
◦ Muscle Contraction
◦ Nervous system
 They are the machines of
the cell. If there’s a job to be
done, it’s likely to involve a
protein.
PROTEIN FUNCTIONS
HISTONE PROTEIN ACTIN PROTEIN Xyn10B
HEME
OXYGEN TRANSPORT
 Hemoglobin protein moves
oxygen around the body.
 Composed of a protein part
called Globin, and a chemical
called Heme.
 Uses an atom of Iron to help
bind to the oxygen atom.
 Hemoglobin is present in large
amounts in red blood cells.
HEMOGLOBIN
CELL SIGNALLING
 Proteins allow for
communication between
cells.
 They act as receptor
molecules, imbedded in
the lipid bilayer of the cell.
 Only interact with specific
molecules.
 Once bound the signal is
sent, and the cells
behavior is modified.
ENZYMES
 Enzymes are globular
proteins.
 They are responsible
for chemical
modification within the
body.
 Similar to an
autonomous robot
working in factory.
 Can add/remove parts,
ENZYMES
 Grab hold of molecules
inside or outside the cell.
 Add or remove individual
atoms.
 Change the structure, which
can result in a variety of
actions:
◦ Convert glucose to ATP
◦ Digest fats, sugars, proteins,
DNA
◦ Repair DNA
◦ Copy DNA
PROTEINS & DISEASE
PROTEINS & DISEASE
 Proteins were not thought to
cause disease.
 Typically associated with
viruses, bacteria, fungi, and
parasites.
 Changed in the 1980’s with the
discovery of Prions by Stanley
Prusiner.
 Demonstrated proteins could
“infect” and self replicate with
requiring any control from
DNA.
PROTEINS & DISEASE
 Proteins now known to be
associated with wide range of
debilitating diseases.
 BSE in cattle, Scrapie in Sheep.
 Huntington’s and Alzheimer's in
humans.
 No cure, no treatment.
 Difficult to diagnose, and difficult
to detect.
 Collectively form Amyloid
Diseases.
PRION PROTEIN (BSE/CJD)
 BSE is caused by a small
protein called PrP (Prion
Protein).
 Small protein associated with
brain cell communication.
 Two types of structure it can
form:
◦ Normal/folded
◦ Abnormal/misfolded
 Abnormal form is very
sticky, results in large build
up protein molecules 
Cytotoxic.
PRION PROTEIN (BSE/CJD)
 Abnormal version of the protein
accumulates in the brain  cell
death.
 For cattle symptoms include:
◦ increased aggression
◦ sensitivity to sound/touch
◦ poor muscle coordination
 For Humans, symptoms include:
◦ dementia, memory loss, hallucinations
◦ problems in speech and movement
◦ seizures
 Patients survive between 2-5
years, but only know after ~1 year.
OTHER AMYLOID DISEASES
OTHER AMYLOID DISEASES
◦ Systemic Amyloidosis
 Build up of protein material in the major organs of the
body
 Heart and Liver are particularly susceptible
◦ Alzheimer’s Disease
 Build of protein material in the brain
 Typically occur later in life, 60’s-70’s
◦ Huntington’s Disease
 Build up of protein in the brain
 Occurs relatively early in life, 30’s
POSSIBLE TREATMENT
 Antibody protein molecules.
 Body utilizes them to attach
invading bacteria and
viruses.
 Bind to protein coats of
viruses/bacteria, alert the
immune system.
 Immune system destroys the
invaders.
BINDS TO VIRUS
ALERTS IMMUNE SYSTE
POSSIBLE TREATMENT
 Antibodies are extremely
selective in what they bind
to.
 Can tailor make them to
bond to anything we want
though.
 So “raise” antibodies to
interact with proteins before
they covert to another
shape.
 Works in theory, not yet a
therapy.
REVIEW
 We ingest protein in our diet, in the form of milk, cheese, meats
and eggs.
 We strip them down to their component parts, use them to make
our own proteins, or energy.
 They have a wide variety of functions in the body.
 Proteins can also cause disease, BSE, CJD, Huntington’s.
 Very difficult to treat, and no known cures.
NEXT WEEK – FATS/LIPIDS
 WHAT ARE FATS?
 STRUCTURE AND
FUCNTION
 FATS AND DISEASE

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Lecture 4 - Proteins and Disease

  • 2.  What are Proteins?  Protein Structure  Protein Function  Diseases Associated with Proteins OUTLINE
  • 3. WHAT ARE PROTEINS? We are exposed to proteins every day of our life. Part of many foods, along with sugar, and fat. Meat, milk, cheese, eggs are all rich in protein. When we ingest protein we break it down into it’s component parts. These parts are used to make proteins we need and want.
  • 4. WHAT ARE PROTEINS?  Machinery of the cell.  Vast array of functions: ◦ Oxygen Transport ◦ Metabolism ◦ Defence ◦ Cell Signalling  Two main types: ◦ Structural & Globular  Made of amino acids.
  • 7. AMINO ACIDS  Proteins are made of small compounds called amino acids.  There are only twenty different amino acid molecules.  Each amino acid is similar in size and composition, but each of them unique.  Amino acids combine to form dipeptides, and polypeptides.  Polypeptides are proteins. PHENYLALANINE TYROSINE ISOLEUCINE
  • 9. 4 LEVELS OF STRUCTURE  A protein molecule has four levels of structure.  Primary  Quaternary.  1° – Amino Acid Sequence  2° – Small Local Structure  3°–Assembly of 2° Structure  4°–Assembly of 3° Structure  Two main types of secondary structure called: ◦ Alpha-helix ◦ Beta-sheet
  • 10. PRIMARY STRUCTURE  Amino acids combine to form a polypeptide.  First step in making protein a protein molecule.  Polypeptides can be as short as 10-20 amino acids, or as long as 1,000 amino acids.  Large amount of variety available in terms of which amino acids are used.  DNA determines which amino acids are used.
  • 11. SECONDARY STRCUTURE  Primary structure of amino acids folds on top of itself to form the secondary structure.  Two main types of secondary structure:  Alpha-helix – hollow tube  Beta-sheet - Flat panel  These structures provides from shape and stability to a protein molecule.  Silk, obtained from larvae of some insects, 5X stronger than steel of the same thickness.
  • 13. TERTIARY STRCUTURE  Alpha helices and beta-sheet structures combine.  Within the same protein molecule you can have both helices and sheets.  Regions of sheet and helix are joined together by flexible regions of linking amino acids.  Proteins are therefore strong but flexible.
  • 14. QUATERNARY STRUCTURE  Some proteins are composed of multiple subunits.  The subunits are identical, and combine to allow the protein to do it’s job.  Allows an extra level of regulation in the protein function.  Example, Hemoglobin protein for transporting oxygen.
  • 16. PROTEIN FUNCTIONS  Vast array of proteins performing a vast array of functions.  Involved in: ◦ Immune system ◦ Oxygen Transport ◦ Eyesight ◦ Muscle Contraction ◦ Nervous system  They are the machines of the cell. If there’s a job to be done, it’s likely to involve a protein.
  • 17. PROTEIN FUNCTIONS HISTONE PROTEIN ACTIN PROTEIN Xyn10B
  • 18.
  • 19. HEME OXYGEN TRANSPORT  Hemoglobin protein moves oxygen around the body.  Composed of a protein part called Globin, and a chemical called Heme.  Uses an atom of Iron to help bind to the oxygen atom.  Hemoglobin is present in large amounts in red blood cells. HEMOGLOBIN
  • 20. CELL SIGNALLING  Proteins allow for communication between cells.  They act as receptor molecules, imbedded in the lipid bilayer of the cell.  Only interact with specific molecules.  Once bound the signal is sent, and the cells behavior is modified.
  • 21. ENZYMES  Enzymes are globular proteins.  They are responsible for chemical modification within the body.  Similar to an autonomous robot working in factory.  Can add/remove parts,
  • 22. ENZYMES  Grab hold of molecules inside or outside the cell.  Add or remove individual atoms.  Change the structure, which can result in a variety of actions: ◦ Convert glucose to ATP ◦ Digest fats, sugars, proteins, DNA ◦ Repair DNA ◦ Copy DNA
  • 24. PROTEINS & DISEASE  Proteins were not thought to cause disease.  Typically associated with viruses, bacteria, fungi, and parasites.  Changed in the 1980’s with the discovery of Prions by Stanley Prusiner.  Demonstrated proteins could “infect” and self replicate with requiring any control from DNA.
  • 25. PROTEINS & DISEASE  Proteins now known to be associated with wide range of debilitating diseases.  BSE in cattle, Scrapie in Sheep.  Huntington’s and Alzheimer's in humans.  No cure, no treatment.  Difficult to diagnose, and difficult to detect.  Collectively form Amyloid Diseases.
  • 26. PRION PROTEIN (BSE/CJD)  BSE is caused by a small protein called PrP (Prion Protein).  Small protein associated with brain cell communication.  Two types of structure it can form: ◦ Normal/folded ◦ Abnormal/misfolded  Abnormal form is very sticky, results in large build up protein molecules  Cytotoxic.
  • 27. PRION PROTEIN (BSE/CJD)  Abnormal version of the protein accumulates in the brain  cell death.  For cattle symptoms include: ◦ increased aggression ◦ sensitivity to sound/touch ◦ poor muscle coordination  For Humans, symptoms include: ◦ dementia, memory loss, hallucinations ◦ problems in speech and movement ◦ seizures  Patients survive between 2-5 years, but only know after ~1 year.
  • 29. OTHER AMYLOID DISEASES ◦ Systemic Amyloidosis  Build up of protein material in the major organs of the body  Heart and Liver are particularly susceptible ◦ Alzheimer’s Disease  Build of protein material in the brain  Typically occur later in life, 60’s-70’s ◦ Huntington’s Disease  Build up of protein in the brain  Occurs relatively early in life, 30’s
  • 30. POSSIBLE TREATMENT  Antibody protein molecules.  Body utilizes them to attach invading bacteria and viruses.  Bind to protein coats of viruses/bacteria, alert the immune system.  Immune system destroys the invaders. BINDS TO VIRUS ALERTS IMMUNE SYSTE
  • 31. POSSIBLE TREATMENT  Antibodies are extremely selective in what they bind to.  Can tailor make them to bond to anything we want though.  So “raise” antibodies to interact with proteins before they covert to another shape.  Works in theory, not yet a therapy.
  • 32. REVIEW  We ingest protein in our diet, in the form of milk, cheese, meats and eggs.  We strip them down to their component parts, use them to make our own proteins, or energy.  They have a wide variety of functions in the body.  Proteins can also cause disease, BSE, CJD, Huntington’s.  Very difficult to treat, and no known cures.
  • 33. NEXT WEEK – FATS/LIPIDS  WHAT ARE FATS?  STRUCTURE AND FUCNTION  FATS AND DISEASE

Editor's Notes

  1. See page 260 of Garrett & Grisham
  2. See page 260 of Garrett & Grisham