Group 3

Understanding
Quaternary Structure
of Proteins
Prepared by: Kian Deuter D. Gacot
I. Introduction
 Two Types of Proteins
• Fibrous Proteins- rope-like, structural
proteins; form shape of cells and tissues.
Ex. Collagen-the most abundant protein of
vertebrates.

• Globular Proteins- these proteins have a

wide range of functions and are relatively
spherical in shape.
Ex. Hemoglobin, Insulin, DNA, etc.

Gacot
 Protein Structure
Primary
Structure Amino acids

Secondary Helix
Structure

Polypeptide Aggregation of two or

chains more polypeptides

Quaternary
Tertiaty
Structure
Structure
Gacot
 Protein Structure

Polypeptide Aggregation of two or

chains more polypeptides

Gacot
II. Definition of
Quaternary
Structure
 A. Explanation of Quaternary Structure

Protein Quaternary Structure

• Is the fourth (and highest) classification level of protein structure.

• It refers to the structure of proteins which are themselves composed of

two or more smaller protein chains (also referred to as subunits).

• It refers to the number and arrangement of the protein subunits with

respect to one another.

Gacot
 A. Explanation of Quaternary Structure

• In contrast to the first three levels of protein structure, not all proteins will
have a quaternary structure since some proteins function as single units.

Ex. proteins that function as single units.

Enzymes, Hormones, Toxins, Chaperones

Gacot
 Protein Structure
An individual proteins in the assembly
are called monomers or subunits.

An association of
two proteins is called a dimer;
three proteins is a trimer;
four is a tetramer;
five is a pentamer;
six is a hexamer.
Gacot
Example: tetramers
 B. Importance of Quaternary Structure in Protein Function

Quaternary structure is an important protein attribute that is closely related to

its function. Proteins with quaternary structure are called oligomeric proteins.

Oligomeric proteins are involved in various biological processes, such as

metabolism, signal transduction, and chromosome replication. Thus, it is highly
desirable to develop some computational methods to automatically classify the
quaternary structure of proteins from their sequences.

Gacasa
III. Protein
Subunits
 A. Definition of Protein
Subunits
The protein subunits are individual components that come together to form
a larger protein complex. In the context of protein, subunits refer to the smaller
units that assemble to create a functional protein molecule. These subunits can
be identical or different in structure and function. When multiple subunits join
together through interaction such as hydrogen bonds, disulfide bonds, and
hydrophobic interaction, they form a complex protein structure with specific
biological functions. The arrangement and combination of these subunits
determine the overall structure and function the protein complex.

Labas
 B. Examples of Protein
Subunits
1. Hemoglobin: It's composed of four protein subunits,
each containing a heme group that binds oxygen.

2. Insulin: Consists of two protein

subunits, A and B chains, linked
by disulfide bonds.

Orcales
 B. Examples of Protein
Subunits
3. DNA Polymerase: A complex enzyme consisting of
multiple protein subunits involved in DNA replication.

4. Immunoglobulins (Antibodies): Composed of two identical

heavy chains and two identical light chains.

5. Ribosomes: Composed of two

subunits, large and small, which come
together during protein synthesis.

Orcales
 B. Examples of Protein
Subunits
6. ATP Synthase: An enzyme complex found in
mitochondria composed of multiple protein subunits that
generate ATP.

7. Photosystem II: A protein complex in

photosynthesis consisting of numerous subunits
involved in light harvesting and electron
transport.

Orcales
 C. Role of Protein Subunits in Quaternary
Structure
The quaternary structure of a protein is the
association of several protein chains or subunits into a
closely packed arrangement. Each of the subunits has it’s
own primary , secondary, and tertiary structure. The
subunits are held together by hydrogen bonds and van der
Waals forces between nonpolar side chains.

The quaternary structure refers to the number and

arrangement of the protein subunits with respect to one
another. Example of proteins with quaternary structure
include hemoglobin, DNA polymerase, ribosomes,
antibodies, and ion channel.

Loking
 D. Hemoglobin as an Example of Quaternary
Structure

Hemoglobin is a protein
found in red blood cells that is
responsible for transporting
oxygen from the lungs to the
body's tissues and organs.

Lactaotao
 Hemoglobin

Lactaotao
Lactaotao
IV. Protein-Protein
Interactions
 A. Types of Protein-Protein Interactions

Protein-protein interactions play a crucial role in various cellular processes

and are essential for the functioning of living organisms. Here are examples
of different types of protein-protein interactions:

1.Direct Interaction: Proteins that physically bind to each other to perform a

specific function. An example is the interaction between insulin and the
insulin receptor on the cell surface, which triggers signaling pathways
regulating glucose uptake.

Gilwa
 A. Types of Protein-Protein Interactions

2. Suppressive Genetic Interaction: Proteins whose combined activity leads

to a phenotype that is less severe than expected based on the individual
effects of each protein. For example, the interaction between the tumor
suppressor proteins p53 and BRCA1, which together help prevent the
development of cancer.

Gilwa
 A. Types of Protein-Protein Interactions

3. Additive Genetic Interaction: Proteins whose combined activity leads to

a phenotype that is more severe than expected based on the individual effects
of each protein. An example is the interaction between proteins involved in
DNA repair pathways, where mutations in multiple genes can lead to
increased genomic instability.

4. Physical Association: Proteins that are found in a complex together but

may not necessarily directly interact. An example is the association of the
ribosomal proteins with the ribosomal RNA to form the ribosome, where the
proteins provide structural support for protein synthesis.

Gilwa
 A. Types of Protein-Protein Interactions

5. Other Associations: This category includes various types of interactions

such as:

- Allosteric Interactions: Proteins that influence each other's activity through

conformational changes. An example is the binding of oxygen to hemoglobin,
which affects the affinity of other oxygen molecule for binding.
- Regulatory Interactions: Proteins that regulate each other's expression or
activity. An example is the interaction between transcription factors and their
target genes, where the transcription factors bind to specific DNA sequences
to regulate gene expression.
Gilwa
 B. Methods to Study Protein-Protein Interactions

There are several methods to study protein-protein interactions:

1. Yeast two-hybrid system: This technique relies on the reconstitution of a

transcriptional activator when two proteins of interest interact in yeast cells.

2. Co-immunoprecipitation (Co-IP): This method involves the use of

antibodies to pull down a target protein along with its interacting partners
from a cell lysate.

Lucas
 B. Methods to Study Protein-Protein Interactions

3. Pull-down assays: In this technique, a bait protein is immobilized on a

solid support and used to capture its interacting partners from a cell lysate.

4. Surface plasmon resonance (SPR): SPR measures changes in refractive

index near a sensor surface to monitor real-time protein interactions.

5. Cross-linking coupled with mass spectrometry (XL-MS): Cross-linking

agents are used to covalently link interacting proteins, and then mass
spectrometry is used to identify the cross-linked peptides, revealing the
interaction sites.

Lucas
 B. Methods to Study Protein-Protein Interactions

6. Fluorescence resonance energy transfer (FRET): FRET measures the

transfer of energy between two fluorophores attached to interacting proteins,
providing information on their proximity.

7. Protein microarrays: Arrays containing thousands of proteins are used to

study protein interactions on a large scale.

Lucas
 C. Significance of Protein-Protein Interactions
in Quaternary Structure

Protein-protein interactions play a pivotal role in determining the stability,

functionality, and regulation of these multi-subunit protein complexes. Understanding
thE functional significance of protein-protein interactions in quaternary structure
provides insights into the complexity and versatility of protein function in biological
systems.

1.Stability and Structural Integrity

2.Functional Diversity
3.Regulation and Allosteric Control
4.Signal Transduction and Cellular Communication
5.Pathophysiological Implications

Francisco
V. Regulation of Protein
Function by Quaternary
Structure
 Discussion of factors influencing quaternary structure

The quaternary structure of a protein refers to the arrangement of multiple

protein subunits coming together to form a functional macromolecular
complex. This assembly is crucial for the protein's biological activity. The
factors that influence the quaternary structure, particularly pH and
temperature, are essential for understanding protein stability and function.

Lequillo
 Discussion of factors influencing quaternary structure

1. PH: The pH of a protein significantly influences its quaternary structure,

affecting the ionization state of amino acid side chains, electrostatic
interactions, hydrogen bonding, and stability. Deviating from the optimal pH
can cause protein unfolding or loss of function.

2.Temperature: affects protein stability by affecting kinetic energy.

Increased temperatures increase protein molecules' kinetic energy, leading to
unfolding or dissociation. Conversely, lower temperatures slow molecular
movement, making it difficult to maintain quaternary structure. Deviations
can cause structural changes and function loss.

Lequillo
THANK YOU!