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Transcript
8/19/08 Fundamentals I Lecture- 11-12:00
*After Break*
Questions during the break:
 Sulfhydryl groups which can be oxidized to form disulfide bonds between cysteine
and cysteine are formed only after the tertiary structure is produced. The two
cysteines can be hundreds of amino acids away from each other and when a molecule
forms into its tertiary structure they are close enough to form a disulfide bond.
Fibrous Proteins- #13
 Helical chains wrapped around each other forming coiled-coils
 Keratin and Myosin
-heptad repeat-very specific side chains moving up cylinder in a diagonal fashion because
they are very large alpha helices (200-300amino acids)
-every 7th amino acid has leucine
 Collagen (triplet repeat, GXY, GPP)- polyproline triple helix
-never  helix or  pleated sheets- this is because of the proline
- long elongated molecule- triplet repeat
-triplet repeat- every third amino acid is glycine
Slide #14
(a) Coiled coil-  helices- place leucine or another hydrophobic amino acid at every 7th
position so hydrophobic side chains are covered up by winding molecules together.
- hydrophobic bonds covered similar to globular, but instead winding and no
spherical collapse.
-remains elongated
Structure of Collagen- #15
 Triple helical Structure:
-Three  chains (but no  helices) each coiled in left-handed sense (purple
strands- polypro line helix)- Minor helix
-Three  chains coiled about each other in right-handed sense- Major helix
H-bonds in the Collagen Fold- #16
 Unwrap collagen helix you see:
 Each chain has a glycine at every 3rd position- 3 chains staggered by one amino acid
 Glycine staggered so at every position of the 3 helices
 Will have as many as 1000-1800 amino acids per chain
 Gets stability from hydrogen bonds and polyproline helix-hydrogen of an amino acid
on one chain is hydrogen bound to a carboxyl group of an amino acid on a
neighboring chain.
 May have other hydrogen bonds using water as an intermediate.
 Uses water-hydrogen bond of hydrogen and oxygen
The Laminin Fold- #17




Has a unique structure- looks like a greek cross in an electron microscope.
Maintenance/structural protein for basement membrane of kidneys and lens capsule
Lens of every eye encapsulated with type IV collagen and laminin.
3 polypeptide chains-  helices wrapped around each other and separate at a certain
point.
Quaternary Structure of Proteins- #1
 Multi-chained protein required for function of protein
 Non- covalent association by globular proteins
-ex: hemoglobin- 4° chains associated by hydrophobic and ionic bonds, so can be
easily dissociated.
 Covalent association by fibrous proteins
-Must be strong because makes up ligaments and tendons in the body.
 Forces: hydrophobic interaction.
Advantages of 4° Association- #2 and #3
1. Stability
-Surface to volume ratio decreases as you increase the volume.
-Surface area increases slower than volume.
-Surface increases by the radius squared.
-Volume increases by the radius cubed.
-More material with less exposure to solute.- advantage because fighting for stability
against aqueous environment.
2. Exclusion of mutated proteins
-If have mutation, subunit will not be incorporated into 4° structure-exception: collagen or other structural proteins- If mutated then nonfunctional
3. Efficiency
-Synthesize small proteins more accurately than a large protein.
-Mistake in 1 of every 400 amino acids- Genome perfect but usage is imperfect.
-Probability of making small molecules greater, so cuts down on mistakes in transcription
or translation.
4. Assembly of catalytic sites is facilitated.
-Have chain with one facet of catalytic site joined with another and you have arranged a
molecule with a specific function and unique and coordinated activities.
-ex: prolyl hydroxylase alpha-beta subunits
-alpha subunits do prolyl hydroxylation
-beta subunits needed to make disulfide bonding
5. Assembly of units with unique and coordinated activities
-Ex: enzymes, hemoglobin- 4 different subunits make the carrying of oxygen possible.
Slide #4
Liver alcohol dehydrogenase- 4° structure-enzyme in liver which converts alcohol to
acetaldehyde- takes hydrogen away from alcohol
 Dimer which has several alpha helices on the surface- amphipathic (one side aqueous,
one core)
 Also has beta pleated sheets- all in core of protein- used to make the dimer
-Blue and Pink cemented together by extending the beta sheet arrangement
Slide #5
 Prealbumin dimer
 Green segments extend and make dimer
 Dimer formed by interaction between beta pleated sheets
 Beta pleated sheets are very useful because they can be as narrow, wide, deep as
needed.
 Around core are a series of loops with no defined structural characteristics.
Slide #6
 Immunoglobulin molecule-quaternary structure
 Derived from 4 separate polypeptide chains: 2 heavy chains and 2 light chains
 Held together by disulfide bonds as also seen with insulin
 Each half circle is a region of chain with much tertiary structure as seen in first hour
of the lecture.
 N termini is where the business end of an IgG molecule is located- loops at this
region are responsible for identifying the nature of the antigen.- Sites of antigen
recognition.
Slide #7
 Tubulin dimer- pathway for structure within a cell
 Alpha and beta chains will line up to form this tubule.
 Quaternary structures composed of aggregated dimers even inside cells- cytoskeleton
 Another example of a quaternary structure is the coat protein of a virus.
Slide #8
 Hemoglobin- quaternary structure formed from subunits which resemble the
myoglobin molecule
 Hemoglobin and myoglobin very related- almost 50% identity in primary structure
 4 subunits held together by hydrophobic and ionic bonds
 Every chain has a heme group (just as in myoglobin)- 4 chains so theoretically
capable of carrying 4 oxygen atoms
 Hemoglobin carries oxygen in body
 Heme group needs to be protected because it is in a poreferron ring
 It is a ferrous iron molecule that would be exposed to solvent but is not because it is
in a hydrophobic region of the molecule in a heme pocket so water can not get to it
 If water were exposed to it, it would oxidize the iron atom and this would make ferric
iron (rusty).
 Iron easily oxidized in aqueous environment- if oxidized it would not be able to carry
oxygen to the tissues.
 Hemoglobin needs to have this protective cavity in order to remain as ferrous iron and
function properly.
Slide #9


Collagen Fibers
Zebra- like appearance- light and dark bands because collagen molecules have a
discreet organization
 Line up in a quarter-staggered array- gives rise to gap region followed by an overlap
region
 Pentafibril molecule- not on powerpoint- located in later lecture notes
-each cylinder is a triple helical molecule
-entire molecule 4.4D in length
 Collagen Fibers associated by hydrophobic binding, which doesn’t need anything
special:
- You could take a solution of collagen fibers at neutral pH in neutral strength solution
(.15M) and hold it in your hand during class, and warmth from hands would cause the
molecules to precipitate and form fibers.- They do this because that is the temperature of
a body.