A protein needs to adopt a final and stable 3-dimensional shape in order to function properly. • The Tertiary Structure of a protein is the arrangement of the secondary structures into this final 3-dimensional shape.

1. TERTIARY STRUCTURES OF
PROTEINS
FORCES STABILIZING TERTIARY PROTEIN STRUCTURES
WARDAH SHAH
ROLL NO. 7
SUBMITTED TO DR. KHALID M FAZILI
DEPT OF BIOTECHNOLOGY
UNIVERSITY OF KASHMIR

2. CONTENTS
• Introduction
• Classification
• Stabilizing forces

3. • A protein needs to adopt a final and stable 3-dimensional shape in order to function properly.
• The Tertiary Structure of a protein is the arrangement of the secondary structures into this
final 3-dimensional shape.
• The sequence of amino acids in a protein (the primary structure) will determine where alpha
helices and beta sheets (the secondary structures) will occur.
• These secondary structure motifs then fold into an overall arrangement that is the final 3-
dimensional fold of the protein (the tertiary structure).Each unique sequence of amino acids
gives rise to a unique protein type, with a unique shape and function.

4. ANFINSENS DOGMA
• Also known as Thermodynamic
Hypothesis
• It states that, at least for a small globular
protein in its standard physiological
environment, the native structure is
determined only by the protein's amino
acid sequence.
• An unfolded protein can go back to its
folded native conformation in favourable
environment due to the properties of its
amino acid sequence.

5. FIBROUS GLOBULAR INTRINSICALLY
DISORDERED
• Fibrous proteins usually consist
of a single type of secondary
structure
• Their tertiary structure is
relatively simple.
• The structures that provide
support, shape, and external
protection to vertebrates are
made of fibrous proteins.
• Globular proteins often
contain several types of
secondary structures.
• Most enzymes are globular
proteins.
• Intrinsically disordered proteins
can lack secondary structure
entirely.
• regulatory proteins can be
globular, disordered, or contain
both globular and disordered
segments.

6. THE STRUCTURE-FUNCTION RELATIONSHIP
• If a protein does not fold correctly it will not function properly. Therefore, researching a protein's
structure is very important when trying to understand what it does and how it works.
• When scientists study a protein they must first determine the sequence of amino acids in the protein
chain (primary structure).
• They use this sequence to predict the presence of any alpha helices or beta sheets (secondary
structure).
• They can then use X-ray crystallography and NMR to determine a protein's full 3-dimensional shape
(tertiary structure).
• Knowing the tertiary structure of a protein is often crucial to understanding how it functions and how
to target it for drug therapy or other medical uses.
• Note: some proteins of similar structure have different functions.

7. FORCES STABILIZING TERTIARY STRUCTURES
•A proteins conformation is
stabilized largely by weak
interactions. These are ~100
folds weaker than covalent
bonds but collectively influence
the 3D structure of proteins
significantly.​
•A protein conformation with
the lowest free energy, is the one
with maximum weak
interactions.

8. HYDROPHOBIC FORCE
• Packing of hydrophobic amino acid in the protein core and hydrophilic
amino acids forming the protein surface leads to a favorable increase
in entropy of water by reducing the solvation layer. (solvation layer
formation disrupts waters hydrogen bonding structure which is
energetically unfavorable)
• This protein folding provides maximum hydrogen bonding partners to
water.

9. VAN DER WAALS INTERACTIONS
• The nonpolar side chains in the core are so close together that short-range van der
Waals interactions make a significant contribution to stabilizing interactions.
• It operates over a limited intermolecular distance, I.e., 0.3 nm to 0.6 nm.
• These attractive intermolecular interactions can be of three types:
i. Permanent dipole - dipole interaction (Orientation effect)
ii. Temporary dipole - permanent dipole interaction (Induction effect)
iii. Temporary/Induced dipole – dipole interaction (Dispersion effect)

10. ORIENTATION EFFECT INDUCTION EFFECT DISPERSION EFFECT
• Electrostatic interaction
between to polar molecules
(d+ and d-)
• This is called Keesom force.
• Temporary dipole induced in a
nonpolar molecule by the
permanent dipole of a polar
molecule near it.
• This is called Debye force.
• Temporary dipole formed in a
nonpolar molecule which
leads to temporary dipole in
another nonpolar molecule
near it.
• This is called London force.

11. HYDROGEN BONDING
• The bond in which an electronegative atom shares a
hydrogen atom with another electronegative atom with a
bound hydrogen, is called a hydrogen bond.
• Presence of hydrogen bonding groups without
partners in the hydrophobic core can destabilize the
protein structure. Hence, polar or charged groups in the
protein interior are hydrogen bonded which stabilize the
framework of the protein.
• Hydrogen bonds have an important role in guiding
protein folding process.
• Examples, amide-carbonyl, hydroxyl-carbonyl, hydroxyl-
hydroxyl H-bond.

12. • Energy: 10-40 kJ/mol
• Approx. Length 1.7-3 A
• Strength of the hydrogen
bond varies with angle of the
hydrogen bond interaction.

13. IONIC INTERACTIONS
• Ionic interactions arise from electrostatic attraction
between two groups of opposite charge.
• Ionic bonds are formed as amino acids bearing opposite
electrical charges are juxtaposed in the hydrophobic
core of proteins.
• Although rare, ionic bonds can be important to protein
structure because they are potent electrostatic
attractions that can approach the strength of covalent
bonds.
• The strength of salt bridge increases as it moves to an
environment of lower dielectric constant (in protein
core).

14. DISULFIDE LINKAGE
• Covalent bond formed between thiol
group of two cysteine residues (cystine
formation)
• This plays an important role in protein
folding and stability.
• They are unstable and cytosol as they
require an oxidizing environment. Eg.,
extracellular proteins (insulin).
• It may form the hydrophobic core with
rest of the weak interactions forming
around it.

15. REFERENCES
• Lehninger Principles of Biochemistry
• https://cbm.msoe.edu/teachingResources/proteinStructure
• https://pubs.acs.org/doi/10.1021/acs.jctc.6b00422
• https://www.bionity.com/en/encyclopedia/Hydrophobic_collapse
• https://www.sciencedirect.com/topics/chemistry/van-der-waals-
force
• http://www2.hawaii.edu/~lesaux/621/ewExternalFiles/NJ%20Lecture
%201-1.pdf

16. THANK YOU