Protein

s.

Function of proteins.
Proteins are very important in living organisms and take
on a variety of forms and functions:
Enzymes.
Antibodies.
Actin and myosin
Collagen.
Keratin
antigens

The structure of proteins.

Proteins are made up of carbon, hydrogen, oxygen and
nitrogen. Sometimes sulphur is present.
Proteins are polymers made up of the monomers called
amino acids.
There are 20 different amino acids.
Amino acids can join up in any order and form an
infinite number of protein molecules.

Amino acids.
Amino acids contain an amino group
(-NH) and a
carboxylic acid group
(-COOH).
Each amino acid has an R group.
There are 20 different R groups and this is the reason
for there being 20 different types of amino acids.

Structure of an amino acid.

R
Group

Amino
group

Carboxylic acid
group

The Genetic Code

NeutralNonpolar
Polar
Basic
Acidic

F
I U
R
S C
T

Haveamine
groups
*Listedas
nonpolarby
sometexts

B A

A
S G
E

UUU
UUC
UUA
UUG
CUU
CUC
CUA
CUG

SECONDBASE

Phe
Leu
Leu

AUU
AUC Ile
AUA
AUGMet/start
GUU
GUC
GUA
GUG

Val

UCU
UCC
UCA
UCG
CCU
CCC
CCA
CCG
ACU
ACC
ACA
ACG

GCU
GCC
GCA
GCG

Ser

UAU
UAC
UAA
UAG

Tyr

Pro

CAU
CAC
CAA
CAG

His

Thr

AAU
AAC
AAA
AAG

Asn

Ala

GAU
GAC
GAA
GAG

Stop

Gln

Lys
Asp
Glu

UGU
UGC
UGA
UGG
CGU
CGC
CGA
CGG
AGU
AGC
AGA
AGG

GGU
GGC
GGA
GGG

Cys
Stop
Trp
Arg
Ser
Arg
Gly*

U
C
A
G
U
C
A
G
U
C
A
G
U
C
A
G

T
H
I
R
D
B
A
S
E

Different
Amino
Acid
Classes
O Cysteine
O
Alanine
H2 N
C

C
H

C OH

Nonpolar

H2 N

Generic
O

Amine
H2 N
O

Aspartic
acid
H2 N
C

H
C

Acid OH

C
HS

Polar

Acid

C OH

O Histidine

H2 N
C

C
O

C OH

?R

C OH

Basic

C
H+N

H
NH
C

C OH
H

Glycine O
C

Valine O

C OH

H2 N
C

C
H

H
C

CH3

H3C

H2N
C

C OH
H

C
H

CH3

Isoleucine O
H2 N
C

H3 C

C
H3C

C OH

C OH
H

C OH
H

C
H3 C

H
PhenylalanineO

C
C

H2 N
H

H2 N

Leucine O

C OH

H2 N

Alanine O
H

Non-Polar
Amino Acids

C OH

H2 N

MethionineO

C
H

H 3C
Tryptophan O
H 2N
C

C OH
H

C
H

Proline O
+
NH H2N
C OH
H2 C
C
H2 C
CH2 H

Polar Amino Acids

Serine O
H2 N
C

C OH

H2N
H

H2 N
C

H2 N

C
HS

Asparagine O

C OH

H
NH2

Glutamine O

HO

H 2N

C OH

C
O

H
NH2

C OH
H

C
O

H
Cysteine O

OH

C OH

H 2N

C OH
H

CH3

HO

Tyrosine O

Threonine O

Acidic Amino Acids

Aspartic O
acid
C OH
H2N
C
H
H
C
C
H
OH

Glutamic O
acid
C OH
H 2N
C
H
H
C
H

C
O

H
OH

Basic Amino Acids

Histidine O
C OH

H2 N
C

C
H+N

H2 N

C
C

Lysine O
C

H
NH
C

H3 N

C
H

N
+

H2 N

C
NH2

C OH
H

H 2N

Arginine O

C OH

Levels Of Protein Organization

Primary Structure - The sequence of amino
acids in the protein
Secondary Structure - The formation of
helices and pleated sheets due to hydrogen
bonding between the peptide backbone
Tertiary Structure - Folding of helices and
sheets influenced by R groups
Quaternary Structure - The association of
more than one polypeptide into a protein
complex influenced by R groups

Levels Of Protein Organization

Primary Structure

MetGlyAlaProHisIleAspGluMetSerThr...

How do two amino acids join together ?

Two amino acids join together by condensation to form
a dipeptide .

A peptide
bond is
formed and
this results in
a dipeptide

What is a polypeptide?
A chain of amino acids is known as a polypeptide.

 Proteins are an important class of

biological macromolecules which
are the polymers of amino acids.
Biochemists have distinguished
several levels of structural
organization of proteins. They
are:

Primary structure
Secondary structure
Tertiary structure
Quaternary structure

PRIMARY STRUCTURE

The primary structure of protein refers to the sequence of amino acids

present in the polypeptide chain.
Amino acids are covalently linked by peptide bonds.
Each component amino acid in a polypeptide is called a residue or
moiety
By convention, the 10 structure of a protein starts from the aminoterminal (N) end and ends in the carboxyl-terminal (C) end.

IMPORTANCE OF PRIMARY STRUCTURE

To predict 20 and 30 structures from sequence homologies with
related proteins. (Structure prediction)
Many genetic diseases result from abnormal amino acid sequences.
To understand the molecular mechanism of action of proteins.
To trace evolutionary paths.

METHODS OF AMINO ACID SEQUENCE DETERMINATION

End group analysis Edman degradation.
Gene sequencing method.

SECONDARY STRUCTURE
Localized arrangement of adjacent amino acids formed as the polypeptide chain
folds.

It consists of

-helix
-pleated sheet
-bends
Non repetitive structures
Super secondary structures

Linus Pauling proposed some essential features of peptide units and polypeptide
backbone. They are:
The amide group is rigid and planar as a result of resonance. So rotation about C-N bond
is not feasible.
Rotation can take place only about N- C and C C bonds.
Trans configuration is more stable than cis for R grps at C

From these conclusions Pauling postulated 2 ordered structures helix and sheet

POLYPEPTIDE
CHAIN CONFORMATIONS
The only reasonably free movements
are rotations around the C -N bond
(measured as ) and the C -C bond
(measured as ).
The conformation of the backbone can
therefore be described by the torsion
angles (also called dihedral angles or
rotation angles)

Animation showing Phi angle rotation at Psi =

0.

Animations showing Psi angle rotation at Phi = 0.

RAMACHANDRAN PLOT
A Ramachandran plot (also known as a Ramachandran diagram or
a [,] plot), originally developed in 1963 by G. N. Ramachandran.
White regions : Sterically
disallowed for all amino acids
except glycine.
Red regions : allowed regions
namely the a-helical and b-sheet
conformations.
Yellow areas : outer limit

ALPHA HELIX
Spiral structure
Tightly packed, coiled polypeptide
backbone core.
Side chain extend outwards
Stabilized by H bonding b/w
carbonyl oxygen and amide
hydrogen.
Amino acids per turn 3.6
Pitch is 5.4 A
Alpha helical segments are found in
many globular proteins like
myoglobins, troponin- C etc.

H bonding

BETA PLEATED SHEET

Formed when 2 or more polypeptides
line up side by side.
Individual polypeptide - strand
Each strand is fully extended.
They are stabilized by H bond b/w N-H

and carbonyl grps of adjacent chains.

2 types
Anti -Parallel

Parallel
N

SECONDARY STRUCTURE

EXAMPLES

The collagen triple helix.

Silk fibroin beta sheet.

BETA BENDS
Permits the change of direction of the
peptide chain to get a folded structure.
It gives a protein globularity rather than
linearity.
H bond stabilizes the beta bend structure.
Proline and Glycine are frequently found
in beta turns.
Beta turns often promote the formation of
antiparallel beta sheets.
Occur at protein surfaces.
Involve four successive aminoacid
residues

NON REPETITIVE STRUCTURES

A significant portion of globular
proteins structure may be irregular or
unique.
They include coils and loops.
Segments of polypeptide chains whose
successive residues do not have similar
and values are called coils.
Almost all proteins with more than 60
residues contain one or more loops of 6
to 16 residues, called loops.

Space-filling model of an loop

SUPER SECONDARY STRUCTURES

(MOTIFS)
Certain groupings of secondary structural elements are
called motifs.

beta-alpha-beta motif

-meander motif

Greek key motif

Beta barrel

TERTIARY STRUCTURE
Tertiary structure is the threedimensional conformation of a
polypeptide.
The common features of protein tertiary
structure reveal much about the
biological functions of the proteins and
their evolutionary origins.
The function of a protein depends on its
tertiary structure. If this is disrupted, it
loses its activity.

DOMAINS
Polypeptide chains containing more than ,200 residues usually
fold into two or more globular clusters known as domains.
Fundamental functional and 3 dimensional structure of
proteins.
Domains often have a specific function such as the binding of a
small molecule.
Many domains are structurally independent units that have the
characteristics of small globular proteins.

The two-domain protein glyceraldehyde3-phosphate dehydrogenase.

NAD+

INTERACTIONS STABILIZING 30 STRUCTURE

This final shape is
determined by a variety of
bonding interactions
between the "side chains"
on the amino acids.
Hydrogen bonds
Ionic Bonds
Disulphide Bridges
Hydrophobic Interactions:

TERTIARY STRUCTURE

DETERMINATION OF TERTIARY
STRUCTURE

The known protein structures have come to light through:

X-ray crystallographic studies
Nuclear Magnetic Resonance studies
The atomic coordinates of most of these structures are deposited in a database
known as the Protein Data Bank (PDB).
It allows the tertiary structures of a variety of proteins to be analyzed and
compared.

QUATERNARY STRUCTURE
The biological function of some
molecules is determined by multiple
polypeptide chains multimeric pro
teins.
Arrangement of polypeptide sub unit
is called quaternary structure.
Quaternary structure of hemoglobin.
Sub units are held together by non
covalent interactions.
Eg: Hemoglobin has the subunit
composition a2b2

Proteins can be divided into groups.

Globular proteins. These are molecules that are often
spherical in shape and have a chemical function eg
enzymes.
Fibrous proteins . These have a structural role . They
give strength or elasticity to a particular tissue eg
keratin in hair.

Haem
group

Haemoglobin is
made up of 4
different
polypeptide
chains.

Haemoglobin molecule
Keratin is a secondary
structure protein. it has
a spiral shape and is
held in position by
hydrogen bonds.

Globular proteins.
Globular proteins have the following characteristics:
Irregular amino acid sequence
Sequence is highly specific and never varies between 2
examples of the same protein.
Polypeptides fold into a spherical shape.
Relatively unstable structure.
Metabolic functions.
Egs enzymes, hormones and haemoglobin.

Enzymes.

Structure and function of globular

proteins.
The shape of a globular protein is very delicate and vital
to its function.
An enzyme has a precise tertiary structure that provides
it with its active site. Any change in the shape of the
active site will stop the enzyme from working.
High temperatures make the molecules vibrate and this
causes the weak hydrogen bonds to break and as a
result the shape changes. The enzyme is denatured and
will not work.

Denaturation of proteins.
The three dimensional shape of proteins is maintained by hydrogen
bonds and ionic bonds which are fairly weak.
Any agent such as heat, acids or alkalis will break these bonds and
cause a change in shape.
With a change in shape the protein can no longer carry out its
function.
Change in the tertiary/quartenary structure breakins of bonds
Denaturated proteins cannot play their role in cells
Denaturation is often irreversible (eg. fried egg yolk cannot be
unfried)
Denaturating agents include acids, bases, detergents, heavy metals

Protein denaturation