Proteins have four levels

of organization
Primary
structure is the
amino acid
sequence
The amino acid sequence is coded
for by DNA and is unique for
each kind of protein
The amino acid
sequence
determines
how the
polypeptide
will fold into its
3D shape
 Biology/Chemistry of Protein Structure

Primary Assembly
STRUCTURE

PROCESS
Secondary Folding

Tertiary Packing

Quaternary Interaction
 Protein Assembly

• occurs at the ribosome

• involves dehydration
synthesis and
polymerization of amino
acids attached to tRNA:

NH+- {A + B  A-B + H O} -COO -

3 2 n

• thermodynamically
unfavorable, with E =
+10kJ/mol, thus coupled to
reactions that act as sources
of free energy
• yields primary structure
 Primary Structure
primary structure of human insulin
CHAIN 1: GIVEQ CCTSI CSLYQ LENYC N
• linear
CHAIN 2: FVNQH LCGSH LVEAL YLVCG ERGFF YTPKT • ordered
• 1 dimensional
• sequence of amino acid
polymer
• by convention, written
from amino end to
carboxyl end
• a perfectly linear amino
acid polymer is neither
functional nor
energetically favorable
 folding!
 Even a slight change in the
amino acid sequence can
cause the protein to
malfunction

For example,
mis-formed hemoglobin causes sickle cell disease
Secondary structure results from hydrogen
bonding between the oxygen of one amino
acid and the hydrogen of another
 Protein Folding
• occurs in the cytosol • tumbles towards conformations
• involves localized spatial that reduce E (this process is
interaction among primary thermo-dynamically favorable)
structure elements, i.e. the • yields secondary structure
amino acids
• may or may not involve
chaperone proteins
 Alpha helix
• William Astbury (1930) studied the fiberous
protins and observed that major PERIODICITY
or repeated units of 5 to 5.5 Ao indicating some
regularity in the structure of these protein.
• Pauling and Corey (1951) found that polypeptide
chain form a right handed helical structure by
simple twist about the alpha carbon
The a-helix
• In the a-helix, the carbonyl
oxygen of residue “i” forms a
hydrogen bond with the
amide of residue “i+4”.

• Although each hydrogen

bond is relatively weak in
isolation, the sum of the
hydrogen bonds in a helix
makes it quite stable.

• The propensity of a peptide

for forming an a-helix also
depends on its sequence.
• Pitch 5.1 A
• A. A residue per turn 3.6
• Helix is rise by 1.5A per A.A
• Right hand helix
• Left hand helix
Secondary structure = local folding
of residues into regular patterns
The b-sheet
• In a b-sheet, carbonyl
oxygens and amides form
hydrogen bonds.

• These secondary
structures can be either
antiparallel (as shown) or
parallel and need not be
planar (as shown) but can
be twisted.

• The propensity of a peptide

for forming b-sheet also
depends on its sequence.
 b turns

• b-turns allow the protein backbone to make abrupt turns.

• Again, the propensity of a peptide for forming b-turns depends

on its sequence.
 The alpha helix is a coiled secondary
structure due to a hydrogen bond every
fourth amino acid
 Secondary Structure
• non-linear
• 3 dimensional
• localized to regions of an
amino acid chain
• formed and stabilized by
hydrogen bonding,
electrostatic and van der
Waals interactions
The beta pleated sheet is formed by
hydrogen bonds between parallel
parts of the protein
 A single polypeptide may have
portions with both types of
secondary structure

Link to video
Proteins have four levels
of organization
 Tertiary structure depends on the
interactions among the R group side chains
 Protein Packing
• occurs in the cytosol (~60% bulk
water, ~40% water of hydration)
• involves interaction between
secondary structure elements and
solvent
• may be promoted by chaperones,
membrane proteins
• tumbles into molten globule states
• overall entropy loss is small enough
so enthalpy determines sign of E,
which decreases (loss in entropy
from packing counteracted by gain
from desolvation and reorganization
of water, i.e. hydrophobic effect)
• yields tertiary structure
 Tertiary Structure

• non-linear
• 3 dimensional
• global but restricted to the
amino acid polymer
• formed and stabilized by
hydrogen bonding, covalent (e.g.
disulfide) bonding, hydrophobic
packing toward core and
hydrophilic exposure to solvent
• A globular amino acid polymer
folded and compacted is
somewhat functional (catalytic)
and energetically favorable 
interaction!
 Types of interactions
• Hydrophobic interactions: amino acids
with nonpolar side chains cluster in the
core of the protein, out of contact with
water

= charged
= hydrophobic
 Types of interactions

• Hydrogen bonds between polar side

chains
 Types of interactions
• Ionic bonds between positively and
negatively charged side chains
 Types of interactions
• Disulfide bridge (strong covalent bonds)
between sulfur atoms in the amino acid
cysteine

Link to video
Proteins have four levels
of organization
Quaternary structure results from
interactions among separate
polypeptide chains.
 Protein Interaction
• occurs in the cytosol, in close proximity to other folded
and packed proteins
• involves interaction among tertiary structure elements of
separate polymer chains
• may be promoted by chaperones, membrane proteins,
cytosolic and extracellular elements as well as the
proteins’ own propensities
• E decreases further due to further
desolvation and reduction of surface area
• globular proteins, e.g. hemoglobin,
largely involved in catalytic roles
• fibrous proteins, e.g. collagen,
largely involved in structural roles
• yields quaternary structure
 For example, hemoglobin is composed of
4 polypeptide chains

Link to video
Quaternary Structure
• non-linear
• 3 dimensional
• global, and across distinct
amino acid polymers
• formed by hydrogen
bonding, covalent bonding,
hydrophobic packing and
hydrophilic exposure
• favorable, functional
structures occur frequently
and have been categorized
Proteins have four levels
of organization
The folding of proteins is aided by
other proteins, called chaperones
• Act as temporary braces as proteins
fold into their final conformation

• Research into chaperones is a

area of research in biology
7.5.1
• Explain the four levels
of protein structure,
indicating the
significance of each
level.
Denaturation results in disruption of
the secondary, tertiary, or
quaternary structure of the protein
 Denaturation
– may be due to
changes in pH, temperature or
various chemicals
 Protein function is lost during
denaturation, which is often irreversible
 3.6.4
• Define denaturation.
Folded proteins are placed
into two general categories
Fibrous proteins have polypeptide chains
organized in long fibers or sheets
• Water insoluble
• Very tough physically,
may be stretchy
 Functions of fibrous proteins

• Structural proteins
function in support
– Insects and spiders
use silk fibers to make
cocoons and webs
– Collagen and elastin
are used in animal
tendons and
ligaments
– Keratin is the protein
in hairs, horns and
feathers
 Functions of fibrous proteins
• Contractile
proteins function
in movement

– Actin and myosin

contract to create
the cleavage
furrow and to
move muscles

– Contractile
proteins move
cilia and flagella
 Globular proteins have their chains
folded into compact, rounded shapes

• Easily water soluble

Functions of globular proteins
• Storage proteins function
in the storage of amino
acids
– Ovalbumin is the protein in
egg whites

– Casein is the protein in

milk, source of amino
acids for baby mammals
Functions of globular proteins
• Transport proteins function in the movement of
other substances

– Hemoglobin, the iron containing protein in blood,

transport oxygen from lungs to other parts of the
body (C3032H4816O872N780S9Fe4)

– Membrane transport proteins such as channels for

potassium and water
Functions of globular proteins
• Hormone proteins function as cellular
messenger molecules that help maintain
homeostasis

– Insulin: sends message “allow sugar into cells”

(when blood glucose levels are high, cells will
transport glucose into the cells for use or storage)

– Glucagon: sends message “we need more sugar in

the blood” (when blood glucose is too low, cells will
release glucose)
Functions of globular proteins
• Receptor proteins allow cells to respond
to chemical stimuli

– Growth factor receptors initiate the signal

transduction pathway when a growth
hormone attaches
Functions of globular proteins
– Cholesterol receptors on the cell
membrane allow LDL to be endocytosed
into the cell
Functions of globular proteins
• Protective proteins function as protection
against disease
– Antibodies combat bacteria and viruses
Functions of globular proteins
• Enzymes speed up chemical reactions
– Amylase and other digestive enzymes
hydrolyze polymers in food

– Catalase converts hydrogen peroxide H2O2

into water and oxygen gas during cellular
respiration
7.5.2
– Outline the difference between
fibrous and globular proteins, with
reference to two examples of each
protein type.

7.5.4
– State four functions of proteins,
giving a named example of each.