Protein Structure
Likando Chababa
Protein Structure
• What are proteins?
• Four levels of structure (primary,
secondary, tertiary, quaternary)
• Protein folding and stability
• Protein denaturation
• Protein misfolding and diseases
What are proteins?
Proteins are polymers of amino
acids joined together by peptide
bonds
Primary Structure
It is the linear sequence of amino
acids
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Primary structure of proinsulin
Secondary Structure
It is the local three-dimensional
arrangement of a polypeptide
backbone
Excluding the conformations (3D
arrangements) of its side chains
a Helix
a helix is right-handed
It has 3.6 residues (amino acids) per
turn
The helix is stabilized by hydrogen
bonding
Between carboxylic group and 4th
N–H group
The amino acid side chains point
outward and downward from the
helix
The core of the helix is tightly
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The right-handed a helix
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b Sheets
Two or more polypeptide chains
form hydrogen bonding with
each other
Also called pleated sheets
They appear as folded structures
with edges
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A two-stranded b antiparallel pleated sheet
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Antiparallel b sheets
Two or more hydrogen-bonded
polypeptide chains run in
opposite direction
Hydrogen bonding is more
stable
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b pleated sheets. (a) The antiparallel b pleated sheets
Parallel b sheets
Two or more hydrogen-bonded
polypeptide chains run in the
same direction
Hydrogen bonding is less stable
(distorted)
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b pleated sheets. (b) The parallel b pleated sheets.
Other secondary
structures
Turns (reverse turns)
Loops
b bends
Random coils
Supersecondary structures or
motifs:
bab motif: a helix connects two
b sheets
b hairpin: reverse turns connect
antiparallel b sheets
aa motif: two a helices together
b barrels: rolls of b sheets
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bab motif b hairpin aa motif
Schematic diagrams of supersecondary structures
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b barrel
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Secondary structure of proteins
(a-helix, b-sheets, loops, turns, random coils)
Tertiary Structure
It is the three-dimensional
structure of an entire
polypeptide chain including side
chains
It is the folding of secondary
structure and side chains
Helices, sheets and side chains
combined to form tertiary
structure
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Tertiary structure of proteins
(Secondary structure + side chains)
Domains
Polypeptide chains (>200
amino acids) fold into two or
more clusters known as
domains
Domains are units that look like
globular proteins
Domains are part of protein
subunits
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One subunit with two domains
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One subunit with three domains
Quaternary
Structure
Many proteins contain two or
more polypeptide chains
Each chain forms a three-
dimensional structure called
subunit
It is the 3D arrangement of
different subunits of a protein
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Hemoglobin is a globular protein
A multisubunit protein is called
oligomer
Composed of a b subunits (4
2 2
chains, 4 subunits)
Two same subunits are called
protomers
Protein folding
Forces that stabilize proteins
Protein denaturation
Forces that stabilize
protein structure
Hydrophobic effect:
Nonpolar groups to minimize
their contacts with water
Nonpolar side chains are in the
interior of a protein
Hydrogen bonding
Electrostatic interactions (ion
pairing):
Between positive and negative
charges
van der Waals forces (weak
polar forces):
Weak attractive or repulsive
forces between molecules
Protein
denaturation
Denaturation: A process in which a
protein looses its native structure
Factors that cause denaturation:
Heat: disrupts hydrogen bonding
Change in pH: alters ionization
states of aa
Detergents: interfere with
hydrophobic interactions
Chaotropic agents: ions or small
organic molecules that disrupt
hydrophobic interactions
Protein misfolding
Every protein must fold to achieve
its normal conformation and
function
Abnormal folding of proteins leads to
a number of diseases in humans
Alzheimer’s disease:
b-amyloid protein is a misfolded
protein
It forms fibrous deposits or plaques
in the brains of Alzheimer’s patients
Creutzfeldt-Jacob or prion disease:
Piron protein is present in normal
brain tissue
In diseased brains, the same protein
is misfolded
Therefore it forms insoluble fibrous
aggregates that damage brain cells
That’s all!