Protein Structure
Amino acids and primary structure
Secondary structure
Tertiary and quaternary structure
Protein Function
Binding and antibodies
Catalysis and enzymes
Mechanical machines
BIOPOLYMERS
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The central dogma of molecular biology
What is a protein?
• A protein is a linear polymer of amino acids linked
together by peptide bonds.
• The average protein is ~200 amino acids long, but
some can contain thousands of amino acids.
• Proteins are the main functional chemicals in the
cell, carrying out many functions.
• Proteins have a complex structure which can be
thought of as having four structural levels.
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What do different proteins do?
1. Enzymes
catalysts of various biochemical reactions
e.g. lactase catalyses the breakdown of lactose into glucose and galactose
(no lactase and you’re lactose intolerant)
2. Hormones
co-ordinate bodily activities
e.g. insulin regulates blood sugar level (if not, diabetes)
3. Receptors
Involved in cellular signalling
e.g. beta-adrenergic receptor responds to adrenaline
4. Defensive proteins
defence against pathogens
e.g. antibodies combat bacteria and viruses
What do different proteins do?
5. Structural proteins
provide structure and support
e.g. collagen in tendons and ligaments, keratin in
hair and nail
6. Storage proteins
e.g. store amino acids; ovalbumin in egg white
7. Contractile proteins
form structures that create movements
e.g. actin fibres in muscles
8. Transport proteins
transport things around body or across membranes
e.g. haemoglobin carries O2 from lung to other body parts
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What is an amino acid?
The main backbone of every
amino acid is the same. This is
what forms the backbone of
the polypeptide chain. It is the
R-group (which projects out
from the backbone) that
makes each of the twenty
kinds of amino acids unique.
Different amino acids have
different properties that affect
the folding of a protein.
R group diversity
The 20 common amino acids have R groups that differ from
each other in the following way:
• Polarity: hydrophobic or hydrophilic or charged
• Charge: positive or negative
• Chemical property: different functional groups
• Size: big or small
• Shape: flat or round
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Amino acid classification
There are 5 groups according to the R group's polarity:
• Nonpolar aliphatic - hydrophobic (i.e. water-hating)
• Aromatic R Group - hydrophobic
• Polar, uncharged - hydrophilic (i.e. water-loving)
• Positively charged - hydrophilic
• Negatively charged - hydrophilic
Non-polar Side chains
The side chain of proline is bonded to both the nitrogen and alpha carbon. The resulting structure
influence protein architecture. Proline is often found in bends of folded proteins. Proline has a
secondary amino group which makes it an imino acid
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Uncharged polar side chains
Acidic Side Chains
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Basic Side Chains
Histidine is often found in the active site
of enzymes where the imidazole ring can
readily switch between states to catalyse
reactions
Each amino acid has a three letter code and a
single letter code:
Alanine Ala A Methionine Met M
Cysteine Cys C Asparagine Asn N
Aspartic Acid Asp D Proline Pro P
Glutamic Acid Glu E Glutamine Gln Q
Phenylalanine Phe F Arginine Arg R
Glycine Gly G Serine Ser S
Histidine His H Threonine Thr T
Isoleucine Ile I Valine Val V
Lysine Lys K Tryptophan Trp W
Leucine Leu L Tyrosine Tyr Y
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Protein Structure
Most proteins are folded into a complex globular shape. Each protein
molecule consists of one or more chains of amino acid monomers.
The amino acids are linked by peptide bonds, so a protein polymer is
often called a polypeptide. Because they are so complicated, proteins
are usually described in terms of four levels of structure.
Primary structure
A protein’s primary structure is the order of amino
acids in the chain. Conventionally written from the
(amino) N-terminal to the (carboxyl) C-terminal.
e.g.
using three letter codes; SER ASP LYS ILE ILE HIS LEU THR ASP ASP SER PHE ASP
or using one letter codes; SDKIIHLTDDSPD
This sequence contains all the information required to
determine the higher levels of structure. The linear
polypeptide chain folds in a particular arrangement,
giving a three-dimensional structure. The information
on how to fold is contained in the sequence.
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Protein Structure
Proteins are polymers
of amino acids.
The peptide bond is planar.
Rotation around the alpha-
carbons leads to a large
number of possible
conformations.
Secondary structure
A regular repetitive conformation of the
polypeptide chain, stabilised by hydrogen bonding
between backbone NH and C=O. The three
dominant forms are;
α Helix
Loop
helix
sheet
loops
β Sheet
Turn
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α-helix
The carbonyl
oxygen of residue n
hydrogen bonds to
the backbone -NH
of the residue n+4.
Side-chains point
away from the helix
axis.
α-helix
The carbonyl
oxygen of residue n
hydrogen bonds to
the backbone -NH
of the residue n+4.
Side-chains point
away from the helix
axis.
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β-sheet
Sheet is held
together by
hydrogen bonding
across the strands.
Side-chains alternate
between pointing up
and down.
β-sheet
Sheet is held
together by
hydrogen bonding
across the strands.
Side-chains alternate
between pointing up
and down.
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β-sheet
loops
Loops join the other
elements of secondary
structure. They are
often solvent exposed.
e.g. thioredoxin has a five stranded beta-
sheet flanked with alpha-helices.
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Relative probability that a given amino acid will
occur in the three common types of
secondary structure
Amino acid sequence affects helix
and β sheet stability
Bulk shape of Asn, Cys, Ser, Thr
can destabilise the helix if they are
close together in a chain.
Proline introduces a destabilising
kink in α helices.
Gly occurs infrequently in α
helices and β sheets as it is very
flexible.
Super secondary structure
Recognisable combinations
(motifs) of secondary structure
βαβ
All β αα corner or helix
turn helix
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Tertiary structure
Describes how elements
of secondary structure
associate to give an
overall protein structure.
Driven by hydrophobic
interactions in the
protein core, salt bridges
and, occasionally,
disulphide bonds.
Tertiary structure
Describes how elements
of secondary structure
associate to give an
overall protein structure.
Driven by hydrophobic
interactions in the
protein core, salt bridges
and, occasionally,
disulphide bonds.
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Domains in tertiary structure
Domains are subdivisions of tertiary structure and are
incorporated as modules into proteins.
β-sandwich
helix bundles Parallel β-barrel
- α/β sequence
Structural domains
can be composed of Myohemerythrin Prealbumin
anything between 25- anti-parallel
300 amino acids. β -sheet
Pyruvate Kinase domain 1
They are often made twisted β-sheet
up of a combination
of motifs
Tobacco mosaic Immunoglobulin Hexokinase domain2
coat protein V2 domain
Quaternary structure
The organisation of
individual protein
subunits into larger
complexes.
Stabilised by the same
types of interaction
that stabilise tertiary
structure
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Quaternary structure
A 90nm diameter
viral shell formed
from an array of
trimers of a single
capsid protein.
chlorella; 5040
copies of a single
protein form the
shell
What do different proteins do?
1. Enzymes
catalysts of various biochemical reactions
e.g. lactase catalyses the breakdown of lactose into glucose and galactose
(no lactase and you’re lactose intolerant)
2. Hormones
co-ordinate bodily activities
e.g. insulin regulates blood sugar level (if not, diabetes)
3. Receptors
Involved in cellular signalling
e.g. beta-adrenergic receptor responds to adrenaline
4. Defensive proteins
defence against pathogens
e.g. antibodies combat bacteria and viruses
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What do different proteins do?
5. Structural proteins
provide structure and support
e.g. collagen in tendons and ligaments, keratin in
hair and nail
6. Storage proteins
e.g. store amino acids; ovalbumin in egg white
7. Contractile proteins
form structures that create movements
e.g. actin fibres in muscles
8. Transport proteins
transport things around body or across membranes
e.g. haemoglobin carries O2 from lung to other body parts
Binding and catalysis
Ligand binding is central to the many biological roles of proteins.
Specificity comes from a binding pocket that is complementary
in size, shape and electrostatic potential surface to the target.
Antibodies bind to foreign ligands to recognise invaders and
tag them for destruction by the immune system
Enzymes, protein catalysts, bind their substrates and products
and accelerate reactions by binding transition states.
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Antibodies
• One function of proteins is to recognise and bind to specific target
molecules - small organic molecules or other macromolecules.
• Antibodies are immune system proteins (immunoglobulins). Each
antibody consists of four polypeptides– two heavy chains and two light
chains joined to form a "Y" shaped molecule.
• They can bind to almost any molecule by adapting the composition of
the variable chains to produce a suitable binding pocket.
• Recognition is achieved by setting up a binding pocket that is
complementary in size, shape and electrostatic potential surface to the
target.
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Enzymes
Free energy
How fast does A go to B?
A With enzyme
How much A goes to B? B
Reaction progress
Enzymes accelerate reactions by stabilising (binding) transition states.
They do not change equilibrium constants.
Types of enzymes-there is international classification of enzymes,
based on the reactions they catalyse.
Class Type of reaction catalysed
Oxidoreductases Oxidation-reduction. A hydrogen or electron donor
is one of the substrates
Transferases Chemical group transfer of the general form
A-X + B to A + B-X
Hydrolases Hydrolytic cleavage of C-C, C-N, C-O and other
bonds (transfer of functional groups to water)
Lyases Cleavage (not hydrolytic) of C-C, C-N, C-O, and
other bonds, leaving double bonds; alternatively,
addition of groups to a double bond
Isomerases Transfer of groups within molecules to yield
isomeric forms (i.e change of geometrical
arrangement of a molecule)
Ligases Formation of C–C, C–S, C–O, and C–N bonds
by condensation reactions coupled to ATP
cleavage
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Machines
Machines; walking along microtubules
Kinesin
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