CHMI 2227E
Biochemistry I
Proteins:
-
Tertiary structure
CHMI 2227 - E.R. Gauthier, Ph.D.
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Tertiary structure
CHMI 2227 - E.R. Gauthier, Ph.D.
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Tertiary structure

Secondary structure:

Involves a single type of structure:




Tertiary structure:

Involves the folding, in space, of the whole
polypeptide chain;

Involves several elements of seconday
structures, whichy interact together through
different interaction forces/bonds:
a-helix
b-pleated sheet
Presence of interactions between amino
acids that are close together in the primary
structure



Main type of interaction: H bonds.

Necessary but not sufficient to make a
functional protein.
Collagen



H bonds
Electrostatic interactions
Van der Waals interactions
Hydrophobic interactions
Disulfide-bonds

Absolutely required for a protein to be active.

Two main types of tertiary structures exist:


Fibrous (e.g. collagen)
Globular (e.g. myoglobin)
myoglobin
CHMI 2227 - E.R. Gauthier, Ph.D.
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Tertiary structure
http://butane.chem.uiuc.edu/cyerkes/chem104A_S07/Lecture_Notes_104/lect28c.html
Interaction forces

For proteins in an
aqueous environment:

Hydrophobic amino acids
are buried in the interior
of the structure;
 Hydrophilic amino acids
are exposed to the
solvent;

Conversely, membranebound proteins are
exposed to an
hydrophobic
environment:

Hydrophobic amino acids
are exposed;
 Hydrophilic amino acids
are buried inside.
Check this one out: http://www.elmhurst.edu/~chm/vchembook/567tertprotein.html
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CHMI 2227 - E.R. Gauthier, Ph.D.
Tertiary structure


Protein folding occurs in specific
steps:

Some individual elements of
secondary structure are first formed;

A few elements of secondary
structure cluster together to form
conserved folding motifs;

These bundles of secondary
structure then form domains, which
fold independently of the rest of the
protein;

Finally, several domains interact to
form the final, functional 3-D
structure of the protein.
Any given protein will always adopt
the same functional 3-D structure.
CHMI 2227 - E.R. Gauthier, Ph.D.
A
B
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Tertiary structure
Folding motifs - 1
CHMI 2227 - E.R. Gauthier, Ph.D.
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Tertiary structure
Folding motifs - 2
CHMI 2227 - E.R. Gauthier, Ph.D.
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Tertiary structure
Protein domains – Pyruvate kinase
Domain 1
Domain 2
Domain 3
CHMI 2227 - E.R. Gauthier, Ph.D.
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Tertiary structure
1. Myoglobin
b-turn
b-turn

Found in muscles

Binds the oxygen
required for aerobic
metabolism;

Associated with a heme
group, which is actually
responsible for binding
oxygen;
Proline
CHMI 2227 - E.R. Gauthier, Ph.D.
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Tertiary structure
1. Myoglobin
Hydrophilic amino acids: Blue
Hydrophobic amino acids: Yellow
CHMI Cross-sectional
2227 - E.R. Gauthier, Ph.D.
view
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Tertiary structure
2. Porin – a membrane-bound protein
Hydrophilic amino acids: Blue
Hydrophobic amino acids: Yellow
CHMI 2227 - E.R. Gauthier, Ph.D.
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Tertiary structure
Chaperones

For some proteins, folding requires the help of other proteins called
chaperones;

Chaperones generally work by binding to exposed hydrophobic
patches on the unfolded protein, preventing aggregation and
irreversible inactivation.
CHMI 2227 - E.R. Gauthier, Ph.D.
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Tertiary structure
Protein denaturation

Proteins can be
denatured by treatments
that destroy the
interaction forces
required for the adoption
of the proper 3-D
structure:





Heat
pH
Solvent
Urea/guadinium: breaks up
H-bonds
b-ME
Check this one out: http://www.elmhurst.edu/~chm/vchembook/568denaturation.html
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CHMI 2227 - E.R. Gauthier, Ph.D.
Tertiary structure
Protein denaturation

The fact that
ribonuclease can be
reversibly denatured
and renatured in vitro
shows that the
information required for
the proper folding of a
protein resides in its
primary structure.
CHMI 2227 - E.R. Gauthier, Ph.D.
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Examples of proteins
1. Green fluorescent protein

Protein found in the jelly fish;

Has the unique property to emit a green light;

Different variants were produced by genetic
engineering to produce red, yellow, cyan, blue
light.

Extremely useful in cell biology: one can tag it to
her/his protein of interest and follow the protein in
the cell using fluorescence microscopy.
CHMI 2227 - E.R. Gauthier, Ph.D.
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Examples of proteins
1. Green fluorescent protein
Light!
CHMI 2227 - E.R. Gauthier, Ph.D.
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Examples of proteins
1. Green fluorescent protein
Nucleus
CHMI 2227 - E.R. Gauthier, Ph.D.
Golgi
apparatus
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Examples of proteins
1. Green fluorescent protein
CHMI 2227 - E.R. Gauthier, Ph.D.
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Examples of proteins
2. Prion proteins
Toxic form = PrPsc
Normal form = PrPc
http://en.wikipedia.org/wiki/Image:Prion.gif
CHMI 2227 - E.R. Gauthier, Ph.D.
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Examples of proteins
2. Prion proteins
Fiber aggregation
CHMI 2227 - E.R. Gauthier, Ph.D.
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Important web site:
http://www.pdb.org/pdb/home/home.do
CHMI 2227 - E.R. Gauthier, Ph.D.
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