2016

PROTEIN STRUCTURE AND

FUNCTION

Prepared by:
Adham Mahmoud Alkhadrawi
Student ID: 3820160086
School of life sciences

Adham Alkhadrawi
Protein Engineering
assignment
11/27/2016

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Protein structure and function

Protein structure:
A-The -Amino acids:
A central carbon atom is attached to:
a- Amino group (NH+3)
b- Carboxyl group (COO_)
c- Hydrogen atom
d- Side chain (R)
Figure (1) shows the basic structure of -amino acids

Figure (1)
Amino acids are classified according to side chains onto 4 groups.

1- Side chains with basic groups (basic amino acids):

These are 3 amino acids: Arginine, lysine and histidine. These are called basic amino acids
because their side chains are proton acceptors, Figure (2).
Figure (2)

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2- Side chains with acidic groups:

Aspartic and glutamic acids. Both contain carboxyl group as part of their side chains. These groups
are deprotonated and have negative charges at pH 7. Shown in figure (3).

Figure (3)

3- Side chains with polar but uncharged groups:

Six amino acids have polar groups in their side chains. Asparagine and glutamine are amide
derivatives of aspartic and glutamic acids. Serine, threonine and tyrosine have hydroxyl groups
(OH) in their side chains. Cysteine is similar to serine but contains sulfhydryl group (-SH) in side
chain. Shown on figure (4).

Figure (4)

4- Side chains with nonpolar groups:

This group contains nine amino acids: glycine which side chain is only a single hydrogen atom.
Alanine, isoleucine, leucine and valine have hydrocarbon side chains. Phenylalanine and
tryptophan have aromatic side chains. Methionine and proline have side chains with unique
features. Methionine side chain contains thio-ester group (-CH2-S-CH3). Proline side chain forms a
part of a five member group including the -amino group. Shown in figure (5).

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Figure (5)

B- The Peptide Bond:

The peptide bond is formed when amino group of one amino acid reacts with carboxyl group of another
amino acid; the resulting chain is called a peptide. This is shown on figure (6). Once amino acids are linked
in a polypeptide chain, they are called amino acid residues. Peptides are classified according to their
weight into oligo peptides, which contain less than 50 amino acids and polypeptides which contain 50 or
more amino acids.

Figure (6)

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C- Primary Structure of Proteins:

Amino acid sequences of proteins can be determined by several methods:

1- Edman degradation:
This method involves the removal of one amino acid from the amino terminal of protein with the
help of phenylisothiocyanate , the resulting amino acid is then identified and the process is
repeated many times until all amino acids are known. However, this process is time consuming.
This is shown in figure (7).

Figure (7)

2- Overlap method:
This method involves that the poly peptide chain is divided into two samples, one is treated with
CNBr which cleaves after methionine, and the other is treated with trypsin which cleaves after
arginine. The resulting fragments are resolved by chromatography and sequenced by Edman
degradation. This is shown in figure (8).

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Figure (8)

3- Mass spectrometer sequence technique:

In this method, protein is separated by electrophoresis, then the resulting lane is sliced and the
protein digested with a specific protease. The resulting peptides are analyzed by HPLC, and then
the primary structure is determined by overlap method. This is shown on figure (9).

Proteins with one polypeptide chain have primary, secondary and tertiary structures, while
those with more than one chain also assume quaternary structure. Rotation around single
bonds allows for the folding of proteins which is essential for their biological roles.
Secondary, tertiary and quaternary structures are supported by a number of weak non-covalent
interactions, which are hydrogen bonds, ionic bonds, hydrophobic interaction and van der
Waals interaction.

1- Hydrogen bonds:
Hydrogen bond is formed when electronegative atom is attached to hydrogen atom which is
attached to other electronegative atom, as in figure (10).

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Figure (10)

Figure (9)

2- Ionic bonds:
The ionic bond is formed by attraction between negatively and positively charged and
negatively charged ionic groups. The ionic bonds are easily broken by pH changes in the
medium.

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3- Hydrophobic interaction:
When nonpolar groups are placed in water, water molecules form organized cages around them.
The formation of these cages is governed by the second law of thermodynamics, which states
that disorder is favored over order, thus entropy tends to force water molecules to be less
arranged, this leads to clustering of nonpolar groups inside big cages of water molecules which is
known as hydrophobicity. This is shown in figure (11).

Figure (11)

4- van der Waals interactions:

These are weak electrostatic interactions between partially positive atom in one groups and a
partially negative atom in another group. van der Waals radius is the distance around the
atom where the attractive and repulsive forces between atoms are in equilibrium. This radius
varies between different types of atoms.

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D- Secondary Structures of Proteins:

1- The -helix:
The -helix is formed when polypeptide chain fold into a helix. Each complete helical turn
extends 0.54 nm along the vertical axis and requires 3.6 amino acid residues. Hydrogen
bonds are located inside the helix. This is shown on figure (12).

Figure (12)

2- The -sheets:
This structure is formed when adjacent polypeptide chains line up side by side, so that the
carboxyl and amino groups of the adjacent chains form hydrogen bonds to produce a flat
structure that is called a -sheet. This is shown on figure (13).

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Figure (13)

3- Loops and turns:

Secondary structures, known as loops and turns, connect -helices and -sheets and allow folding
of polypeptide chain back on itself in the reverse direction. The most common form is -turns.
There are two types of -turns; type I and type II. In both types there is a hydrogen bond between
n and n+3 residues, this is shown on figure (14).

4- Super-secondary Structures:
These are found in many different proteins, and are formed by certain combinations of different
secondary structures e.g. -helices, -sheets and -turns, as shown on figure (15).

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Figure (14)

Figure (15)

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E- Tertiary Structures of proteins:

The primary structure of a protein determines its tertiary structure. Weak non-covalent bonds can be
disrupted by heat, acids and detergents such as urea and 2-mercaptoethanol. The disruption of tertiary
and secondary structures of proteins is called denaturation, and denatured proteins lose their biologic
activity. Some proteins can renature (undergo renaturation) after being denatured, for example:
Pancreatic ribonuclease A. The addition of urea and 2-mercaptoethanol disrupts disulfide bonds. After
removal of urea and 2-mercaptoethanol, the enzyme retains its tertiary structure again by formation of
typical disulfide bonds, as shown on figure (16).

Figure (16)

This observation proves that at least for ribonuclease A, the tertiary structure is determined by primary
structure. In cells, specific proteins called Molecular Chaperons help other proteins to acquire their typical
folding pattern. Chaperons stabilize newly emerged proteins until they complete the folding process and
then released by ribosome as shown on figure (17).

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Figure (17)

Two enzymes; protein disulfide isomerase and peptidylprolyl cis-trans isomerase, speed the polypeptide
folding of proteins by catalyzing the formation of disulfide bonds and the isomerization of amino acid
proline peptide bonds, as shown on figure (18).

Figure (18)

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Protein Function
1- Proteins provide structural support to cells:
In the form of microtubules and actin filaments, proteins provide mechanical support to cells.
Actin filaments also help for cell locomotion in prokaryotes and in mitotic spindle, as shown on
figure (19).

Figure (19)

2- Proteins catalyze biochemical reactions of a cell:

Thousands of enzymes are working to catalyze every metabolic reaction in living cells. They allow
for reaction to occur at thousand or million times faster than reactions without enzyme catalysis.
Enzymes are so specific for certain substrates and catalyze only certain metabolic reactions.

3- Proteins carry out important functions in plasma

membranes:
Proteins transport nutrients across cell membrane, receive chemical signals from outside the cell,
translate signals to intracellular actions and help anchoring cells to a certain location, as shown on
figure (20).

Figure (20)

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References:
Anfinsen, C. B. (1972). Studies on the principles that govern the
folding of protein chains.
Barton, G. J. (1995). Protein secondary structure prediction.
Current opinion in structural biology, 5(3), 372-376.
Branden, C. I. (1999). Introduction to protein structure. Garland
Science.
Chan, H. S. (2002). Amino Acid Sidechain Hydrophobicity. eLS.
Deber, C. M., Brodsky, B., & Rath, A. (2001). Proline Residues in
Proteins. eLS.
Gilbert, H. F. (2010). Peptide Bonds, Disulfide Bonds and
Properties of Small Peptides. eLS.
Smith, J. B. (2001). Peptide sequencing by Edman degradation.
eLS.