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Slide 1
Module 7 – Protein structure

Dr Lakshmi Wijeyewickrema

Department of Biochemistry and Genetics Slide 2

Intended Learning Outcomes
(ILOs)
After this lesson students will be able to:

• Understand the basis for tertiary structure in proteins.

• Understand the formation of tertiary structure of proteins.
• Describe the tertiary structure of myoglobin.
• Understand the significance of domains in protein function.

Slide 3
 Tertiary structure
• the overall three-dimensional shape of a protein that
results from the interactions between amino acid side
chains (R groups) that are widely separated from each
other within a peptide chain.

Slide 4
 Why do proteins have well-defined
structure?
• The sequence of amino acids in a protein (usually) suffices
to determine its structure.
• A chain of amino acids (usually) “folds” spontaneously
into the protein’s preferred structure, known as the “native
structure”
• Why? – Intuitively: some amino acids prefer to be inside,
some prefer to be outside, some pairs prefer to be near
one another, etc.

Slide 5
Interactions Responsible for Tertiary
Structure

Slide 6
 Myoglobin

• Myoglobin is a relatively
small (Mr 16,700), oxygen-
binding protein of muscle
cells that functions in the
storage and transport of
oxygen for mitochondrial
oxidation of cell nutrients.
• Myoglobin consists of a
single protein chain with
153 amino acids and one
heme group that stores
oxygen in the muscle cells.

Slide 7
 Myoglobin

• Myoglobin is an extremely
compact molecule where the
about 70% of the main chain
is folded into eight alpha-
helices, and much of the
rest of the 30% of the chain
forms turns and loops
between the helices. 
• O2 binding pocket is formed
by a heme group and
specific amino acid side-
chains that are brought into
position by the tertiary
structure

Slide 8
 Myoglobin
• The surface contour
picture shows the binding
pocket for the heme
group
• Globular nature of the
protein is clearly seen

Slide 9
Myoglobin
• Hydrophobic groups
(blue) are hidden in the
interior of a globular
protein
• Above the ball and stick
hydrophobic groups are
clearly seen, in space
filling model below the
groups are mostly hidden
• Note also how the heme
group is buried in its
pocket.

Slide 10
Department of Biochemistry and Genetics Slide 11
 Cytochrome c

• Metalloprotein - contains a
heme group
• Part of the respiratory chain
• consists of a-helices
• 40% of Aa are in a-helices
• Heme group is in a special
groove

Slide 12
 Lysozyme
• Enzyme found in
secretions (eg. Tears)
• Anti-bacterial
• Cleaves polysaccharides
in bacterial cell walls
• Mostly a-helix, but also
some b-sheet
• Note turns connecting
sheets and helices
• Active site is in groove of
the molecule
• 4 disulfide bonds

Slide 13
 Ribonuclease

• Enzyme cleaving
ribonucleic acids in the
diet
• Mixture of a-helices and
b-sheets
• 4 disulfide bonds
• Note active site groove

Slide 14
 Protein Domains
• A domain is a basic structural unit
within a protein molecule.
• Part of a protein that can fold into
a stable structure independently.
• Different domains can possess
different functions.
• Proteins can have one to many
domains depending on protein size.
• Domains are usually connected
with relatively flexible areas of
protein.
• One polypeptide chain can form
multiple domains Pyruvate kinase, a protein
with three domains
Slide 15
 Domain example: Src Kinase
3 “domains”, 4 separable parts
Don’t memorize Src Kinase; know domain concepts

• Domains can be functional:

SH2, binds phosphotyrosine
SH3, binds polyproline sequence
Kinase: transfers phosphate from ATP to side chain
Slide 16
 Summary

• The complete 3-dimensional shape of the entire protein (or

sum of all the secondary structural motifs) is known as
the tertiary structure of the protein and is a unique and
defining feature for that protein.
• Primarily, the interactions among R groups creates the
complex three-dimensional tertiary structure of a protein. 
• The structure of the globular protein Myoglobin was the first
breakthrough in understanding the 3-dimensional structure of a
protein.
• Domains are distinct functional and/or structural units in a
protein that can exist in a variety of biological contexts.

Slide 17
Resources

• Lehninger Principles of Biochemistry Seventh

Edition (2017), W. H. Freeman and Company •
Chapter 4.3

Slide 18