Fibrous Proteins

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Fibrous Proteins

• Theyre elongated with usually one dominant form
  of secondary structure. They usually function as
  structural elements of an organism. Some
  examples
• Bones, Teeth, and sinewy Tendons - Collagen, a
  3-helix coiled-coil.
• Lungs and ligaments - Elastin, a springy thing.
• Fur and Claws - a Keratin, a 2-helix coiled-coil.
  
• Silk - Fibroin - a b pleated sheet.

(Note Beowulf reference)
10/1/01
Your Host and MC Alec and his banjo-playin
walrus
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Collagen - our most abundant protein.

• It makes up the stress bearing elements of skin,
  bone, teeth, tendons, etc. etc.
• When mixed with sugar it makes a delicious snack!
  
• (Jello brand Collagen)
• Can be made as a gel goopy part of the eye
• Or as tight bundles of fibers tendons
• Or as a foundation for bones bones - sort of a
  skeleton for a skeleton.
• Collagen is always post-translationally modified
  That is, the protein is chemically modified after
  it is made.

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Collagen - our most abundant protein.

• Collagen has a fascinating
• amino acid composition
• 1/3 Glycine.
• 15-30 proline and
• hydroxyproline.
• Then a dash of other amino
• acids for taste.

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What is Hydroxyproline?
After collagen is synthesized in the ribosome,
certain proline residues are hydroxylated at the
C-4 position by prolyl hydroxylase. Prolyl
hydroxylase needs ascorbic acid (Vitamin C) for
activity. Deficiencies in Vitamin C lead to loss
of this modification. Without this modification,
collagen denatures at body temperature. Thats
what we call SCURVY.
Argh!
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Glycine every third residue?
What do you get when you mix glycine and proline
with a periodicity of three residues?
Linus Pauling would know.
Got that straight, bully-boy!
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A polyproline/polyglycine helix!

• Lets review
• Seen in polyproline and polyglycine.
• A left-handed helix.
• Three residues per helical turn!
• Now
• Each collagen molecule is composed of three
  polypeptides.
• With some X-ray data and some clever model
  building, we get ...

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Collagen A triple helix
Each helix is a left-handed polyproline II
helix. Three helices are wrapped into a
right-handed superhelix.
Glycine is required at every third position to
accommodate the close association of the helices.
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Collagen comes in a number of your favorite
flavors.
Slightly different amino acid compositions result
in different properties of the molecule.
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Collagen is secreted
Secreted proteins have a signal at their
N-terminus that tells the ribosome to squirt the
protein into the endoplasmic reticulum. In the
rough ER, the chain is modified as it is
synthesized.
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Collagen has end bits that help it form the
triple helix.
Once the triple helix is formed, the whole thing
is secreted through the golgi.
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Once outside the cell, those helpful end bits are
thrown away like yesterdays laundry.
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Collagen molecules pack to form fibrils.
The naked triple helix self assembles with its
brethren and sistren to form tight bundles.
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Fibrils are further modified to add strength.
Once the fibrils are formed, the lysines on
neighboring molecules become cross-linked
together forming a tough, covalent protein rope.
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Problems in collagen synthesis.

• Inherited problems occur in any number of steps
  in synthesis.
• Ehlers-Danlos syndrome - A number of causes.
  Results in streachy skin and loose joints.
• Osteogenesis imperfecta - A number of causes.
  Effects are seen in bone formation. Bones are
  easily bent or fractured.

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Elastin - the Spandex of Life.
Elastin is a long, stringy polypeptide with an
irregular amino acid structure that is primarily
composed of small, non-polar amino acids (Ala,
Val, Gly) as well as Pro and Lys. The
polypeptide is basically a slinky or a spring
with lysines dotted along the way. What do you
do with Lysines if youre a connective tissue?
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You cross-link it!
Again, lysines are used to hitch-up elastin
molecules to each other. But rather than
hitching them up in a regular array like a
collagen fibril, they are hooked up in a very
disorganized pile of spaghetti. What do you get
when you take a pile of slinkys and tie them
together in a random tangle?
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Molecular Spandex!
Good for Lung walls Vessel walls Elastic
Ligaments
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What could go wrong with Spandex?
Your neutrophils have a taste for elastin.
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Whats Fur Made Of?
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a-Keratin
The sequence of the central 310 residues of
keratin has a 7-residue pseudo-repeat. The first
and fourth residue are hydrophobic. 7 residues
2 turns of an a-helix.
The heptad-repeat forms an a-helix with a
hydrophobic stripe. Two helices associate in a
coiled-coil.
Remember kids Heptad-repeat Coiled Coil!
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Behold the Power of Cysteine
Cysteines are special little guys because their
sulfhydryl group can react with other cysteines
to form covalent disulfide bonds. These bonds are
often important in holding together protein
structure.
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Coiled-Coil is springy in the skin, Cystines make
it hard for CLAWS and hair.
Claws and hair have a high sulfur content from
Cys which rigidifies these tissues. You can
rearrange the cys-cys bonds in your hairs
keratin by adding reducers. Just be careful!
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Silk Fibroin
Silk is made from the cocoons of the silkworm. It
is extremely strong, yet flexible. The sequence
of silk is largely made of the repeat Gly-Ser-G
ly-Ala-Gly-Ala. Alternating Glycines! That has to
be important.
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Silk is made from a b pleated sheet.
Alternating Glycines! Strength along fiber
results from extended, covalent peptide chain
along the fiber axis. Loose associations between
sheets allow flexibility in the fiber.