 Super
secondary Structures (Motifs); The term
motif refers to a set of contiguous secondary structure
elements that either have a particular functional
significance or define a portion of an independently folded
domain.
 Or small, distnct, specific aggregates of secondary
structures .
Super Secondary structure composition,
e.g. all , all , segregated +,
mixed / .
α-amylase inhibitor
Serum albumin
Ferritin
Pilin
Immunoglobulin
Definition; It refers to the folding of the polypeptide chain into a
compact three dimensional structure , or it refers to the spatial
arrangement of amino acid residues which are far apart in the
amino acid linear sequence , and how they interact with each
other, leading to the folding of the polypeptide chain into a 3
dimensional structure. Example Myoglobin.
Stabilizing bonds; Include a large number of weak non-covalent
bonds such as , Hydrogen bonds, ionic bnds , hydrophobic
interactions, vander-Wall forces.
Tertiary structures usually obtain a globular shape.
The three dimensional structure of a protein is determined by its
primary structure (its amino acid sequence in the polypeptide
chain) which determined by it’s specific coding gene.
 The
interactions
of the R groups
give a protein
its specific
threedimensional
tertiary
structure.
5

Covalent bond between
sulfur atoms on two
cysteine amino acids
• Ions on R
groups form
salt bridges
through ionic
bonds
H
Hydrogen
bond
bonds weak
allowing to be
broken and
reformed easily

Allows structural
change

produces ‘functional’
molecules
Tertiary Structure
Proteins that are composed of more than one polypeptide chain
(subunit)show a fourth level of protein structure
Which is the quaternary structure .
Definition ; It refers to the manner in which individual
polypeptide chains interact or fit with each other to form an
oligomeric protein molecule which resembles the functional
unit.
Stabilizing bonds; Include a large number of weak non-covalent
bonds such as , Hydrogen bonds, ionic bnds , hydrophobic
interactions, vander-Wall forces.
The subunits in the quaternary structure can be identical or
different in structure. Two kinds of quaternary structures:


a) homo (dimer, trimer,….ect) protein, when the subunits are
identical.
b) hetero (dimer , trimer ….ect)protein when the subunits are
different.
The subunits may function independently or cooperatively as in
Hb.
Domains are the fundamental functional and
three-dimensional structural units of polypeptides
 Polypeptide chains that are greater than 200
amino acids in length generally consist of two or
more domains
 The core of a domain is built from combinations of
supersecondary structural elements (motifs)
 Folding of the peptide chain within a domain
usually occurs independently of folding in other
domains
 Therefore, each domain has the characteristics of
a small, compact globular protein that is
structurally independent of the other domains in
the polypeptide chain.









It is located in the muscle tissue and is responsible for its brown
color.
Its function is to store and transport oxygen in the skeletal
muscles.
It is a relatively small protein made up of a single polypeptide
chain that contains 153 amino acid residues .
It contains a heme group (which is a prosthetic group consisting
of a protoporphyrin organic ring and a central iron atom).
It is the heme group which is responsible for the oxygen binding
capacity of Myoglobin.
Myoglobin is very similar to Hemoglobin in both its function and
structure ( since both are capable of oxygenation and
deoxygenation).
Myoglobin is an extremely compact molecule(in its interior there
is room for only 4 H2O molecules)
The backbone of the polypeptide chain is made up of 8 segments
of α-helical structures , the largest segment has 23 a.a while the
shortest 7 a.a residues .

Thus 70% of the main polypeptide chain in myoglobin is involved
in α-helical structures.

The rest of the polypeptide chain is loops or bends between the
α-helical segments.

The non-polar amino acids are arranged in the interior (e.g Leu,
Val, Phe)thus producing a hydrophobic interior.

The polar or charged amino acids( e.g Glu, Asp , ) are located on
the outer surface , except for 2 His residues which are in the
interior since they play a critical role in binding iron.

The pro residues and other non-helical a.a residues occur only at
the bends that link the α-helical segments together.

The heme group of myoglobin sits in a cleft in the interior of the
molecule lined with non-polar a.a (except for the 2 His).

There are 2 His in the interior of the myoglobin molecule , the
proximal His which binds directly to the iron atom , the second
His does not interact directly with the heme group , but helps
stabilize the binding of the O2 to the ferrous atom.

Hemoglobin is an oligomeric protein which is composed of 4
polypeptide chains .

Each poypeptide chain has a heme prosthetic group attached to
it in which the iron atom is in the fe2+ state .

The protein part of hemoglobin is called globin which consists of
2 α chains (141 amino acid residue) and 2β chains (146 amino
acid residues).

It is roughly spherical with a 5.5 nm diameter.

The single polypeptide chain (subunit) resembles in its structure
the structure of myoglobin , thus the α and β chains contain
several segments of α-helix separated by bends.

Each heme is partially burried in a hydrophobic pocket lined with
non-polar amino acids.

The heme group is bound to its poypeptide chain through a
coordination bond of the iron atom to the R- group of the
proximal His residue.
Structure of the heme group ;

It consists of a complex organic ring structure (protoporphyrin)
which is a tetrapyrrol ring linked by four methene bridges
( =CH groups) .

It contains methyl , vinyl ,propionic acid groups attached to the
pyrrol rings.

The non-polar vinyl group is burried in the hydrophobic interior
while the hydrophilic groups of the propionic acid projects out of
the pocket to the outside.

The iron atom has 6 coordination bonds four in the plane of the
portophyrin ring and attached to it by binding to the 4 central
nitrogen atoms , the two remaining coordination bonds are
perpendicular to the heme plane where one will bind to nitrogen
atom of the proximal His residue and the other will bind the O2
molecule.
Hemoglobin undergoes conformational changes on binding
oxygen;
The Hemoglobin molecule can presume two major conformations,
the R-state (relaxed state) , and the T-state (tensed state).
Although Oxygen can bind to both conformations but it shows a
significantly higher affinity towards the R-state.
The T-state is stabilized by a number of ionic bonds between the
(α1β1 ) and (α2β2 ) dimers.
The binding of oxygen to a hemoglobin subunit in the T-state
triggers a conformational change to the favored R-state , through
the breaking of some of the ionic bonds with the formation of
some new ones.
Oxygen binding to hemoglobin;

A plot of % saturation of hemoglobin against pO2
(oxygen partial pressure) is sigmoidal , whereas that of myoglobin is
hyperbolic.

This sigmoidal curve of hemoglobin means that hemoglobin has
relatively low affinity for binding the first one or two O2
molecules but once they are bound the binding of subsequent
oxygen molecules is increased (cooperative O2 binding).

Conversly the loss of one O2 molecule from the fully oxygenated
Hb Causes the rest to dissociate more easily when pO2 is
decreased.

The myoglobin hyperbolic curve shows that myoglobin has a
higher affinity towards O2 compared to Hb.

A protein with high affinity to O2 will bind efficiently in the lungs
but will not easily release it in the tissues.

Thus myoglobin cannot carry O2 from the lungs to the tissues as
Hb.

On the other hand the lower affinity seen in Hb suits its function
since it enables to bind O2 efficiently in the lungs where the pO2
Is high and release the O2 easily at the tissues where the pO2 is
decreased.
The Bohr Effect;

The effect of pH on the O2 - Hb
effect ;

HHb + O2
equilibrium is called the Bohr
HbO2 + H+ .
When hb is oxygenated it ionizes to free one H+
as seen in the equation.
for each O2 bound
Since the reaction is a reversible reaction , increasing the [ H+ ] will
cause the equilibrium to shift to the left releasing the O2 .
The relationship between pH and the Hb %Oxygen saturation is
directly related .
This pH effect and the sigmoidal property of Hb allows it to carry O2
Efficiently .
In the lungs where the partial pressure of O2 is high approximately
100 mm Hg , and the pH is also high 7.4 ,the environment favors
the binding of O2 .

Whereas at the tissues where the pO2 is lower and the pH is lower
deoxygenation of Hb is favored.