Protein
Structure Editing File
Color Index:
- Main Text (black)
- Female Slides (Pink)
- Male Slides (Blue)
- Important (Red)
- Dr’s Notes (Green)
- Extra Info (Grey)
Objectives
Understand the peptide bonding between amino acids.
Explain the different levels of protein structure and the forces
stabilizing these structures and what happens when the protein
is denatured.
Define the α-helix and β-sheet as the most commonly
encountered secondary structures in a protein molecule.
Correlate the protein structure with function with hemoglobin
as an example.
Understand how the misfolding of proteins may lead to
diseases like Alzheimer’s or prion disease.
What Are Proteins?
Proteins are large, complex molecules that play many critical
roles in the body.
● Proteins are made up of hundreds or thousands of smaller
units called amino acids, which are attached to one another
in long Chains.
● There are mainly 20 different types of amino acids that can
be combined to make a protein.
● The sequence of amino acids determines:
- Each protein’s unique three dimensional (3D) structure.
- The protein’s specific function
What Are Proteins?
Proteins can be described according to their
large range of functions in the body eg:
1- Antibody
2- Enzyme
3- Messenger
4- Structural component
5- Transport and storage
Primary structure
● It is the linear sequence of amino acids.
How to
determine ● Covalent bonds in the primary structure
the primary of protein:
structure - Peptide bond.
Sequence? - Disulfide bond (if any) (connects 2
residues of cysteine).
● DNA
sequencing ● The primary structure is the simplest
(indirect) and first-level form of structure.
● Direct ● Peptide bonds are very strong and they
amino acids require enzymes to be broken.
sequencing
Peptide Bond (Amide Bond)
● Each amino acid in a chain makes 2 peptide bonds.
● The amino acids at the two ends of a chain make only 1
peptide bond.
● The amino acid with a free amino group is called amino
terminus or NH2-terminus.
● The amino acid with a free carboxylic group is called
carboxyl terminus or COOH-terminus
Residue: the molecule after remove water molecule
Peptides
NOTE 438:
● Residue: amino acid in
polypeptide chain
● We always read from
N-terminus to C-terminus
Note:
● Tripeptide has 2 peptide
bonds
Peptide bond=Amide bond
Peptides
Amino acids can be polymerized to form chains:
• Two amino acids ➔ dipeptide ➔ one peptide bond.
• Three amino acids ➔ tripeptide ➔ two peptide bonds.
• Four amino acids ➔ tetrapeptide ➔ three peptide bonds.
• Few (2-20 amino acids) ➔ oligopeptide.
• More (>20 amino acids) ➔ polypeptide.
How to determine the primary structure sequence?
- DNA sequencing.
- Direct amino acids sequencing.
Secondary structure
● It is regular arrangements of amino acids that are located
near to each other in the linear sequence.
● Excludes the conformations (3D arrangements) of its side
chains.
● α-helix, β-sheet and β-bend are examples of secondary
structures frequently found in proteins.
Secondary structure
α-helix:
● It is a right-handed spiral, in which side chains of amino
acids extended outward.
● Hydrogen bonds: Stabilize the α-helix. form between the peptide
bond carbonyl oxygen and amide hydrogen.
● Amino acids per turn: Each turn contains 3.6 amino acids.
Secondary structure
Amino acids that disrupt an α-helix:
● Proline ➔ imino group, interferes with the smooth helical structure.
● Glutamate, aspartate, histidine, lysine or arginine ➔ form ionic
bonds.
● Bulky side chain, such as tryptophan.
● Branched amino acids at the β-carbon, such as valine or
isoleucine.
Secondary structure
β-sheet: β-sheet:
- Antiparallel
Composition: - Parallel
● Two or more polypeptide chains
make hydrogen bonding with
each other
● Also called pleated sheets
because they appear as folded
structures with edges
Hydrogen bonds in parallel direction are less
stable than in antiparallel direction
Other Secondary
Structure Examples
1- β-bends (reverse turns) Proline is in the β-bends
● Reverse the direction of a polypeptide chain frequently because it
● Usually found on the surface of the molecule and bends due to its imino
often include charged residues group.
● The name comes because they often connect
successive strands of antiparallel β-sheets Glycine: is the smallest
● β-bends are generally composed of four amino amino acids which makes it
acids residues, proline or glycine are frequently easier to bend.
found in β-bends
2- Non-repetitive secondary
E.g. loop or coil conformation
Supersecondary Structure (Motifs)
Supersecondary structure is a combination of secondary structural
elements, such as:
α α motif: β α β motif: β barrels: β hairpin:
01 02 03 04
two α helices a helix rolls of β sheets reverse turns
together connecting two connecting
β sheets antiparallel β
sheets
Tertiary Structure
Tertiary structure: the three-dimensional (3D) structure of an entire
polypeptide chain including side chain (R).
Domains: the fundamental functional and 3D structural units.
Polypeptide chains that have >200 amino acids have 2 or more domains.
The core of a domain: is built from combinations of supersecondary
structural elements (motifs) and their side chain.
Domains can combine to form tertiary structure
Tertiary Structure
Interactions stabilizing tertiary structure:
● Disulfide: SS (Cysteine with Cysteine covalent bond).
● Hydrophobic interactions: between nonpolar amino acids
in the interior of the polypeptide (most important
interaction that stabilizes the tertiary structure)
● Hydrogen bonds: between polar and hydrophilic amino
acids.
● Ionic interactions: oppositely charged side-chains groups
reactions
Protein Folding
Primary structure Secondary structure Supersecondary Tertiary Structure
Structure
- Some proteins Chaperons:
exist in - Specialized group of proteins, required for the
quaternary proper folding of many species of protein
structure (level - Chaperons interact with polypeptides at various
of folding after stages during the folding process
tertiary)
- Chaperons are ● Also known as “heat shock”
folded by proteins ﻷﻧﮫ ﯾزداد ﻋﻧد وﺟود اﻟﺣرارة
other
chaperons. ● They make sure that the folding process is done right
Quaternary Structure
● Some proteins contain two or more polypeptide chains that may be structurally
identical or totally unrelated
● Each chain forms a 3D structure called subunit.
● According to the number of subunits: Dimeric, Trimeric, multimeric
● Subunits may either function independently of each other, or work
cooperatively, e.g. hemoglobin
NOTE441:
● Protein has 1 polypeptide chain → the protein has 3 levels of structure only
(primary,secondary,tertiary).
● Protein has >1 polypeptide chains → the protein has 4 levels of structure (primary,
secondary, tertiary, quaternary).
● Nascent protein: the primary structure of a protein.
● Native protein: the mature protein that has been folded.
● The quaternary structure is the last complexity.
Quaternary Structure
441 Illustration
Hemoglobin
1- Globular protein (round/spherical)
2- α₂ and β₂ (4 subunits)
3- Oligomer (Multisubunit protein)
4- two identical subunits are called
proteomes
Denaturation of Proteins
● Denaturation results in the unfolding and disorganization of the
protein’s secondary and tertiary structures.
● Most proteins, once denatured, remain permanently disordered
● Denatured proteins are often insoluble and, therefore, precipitate
from the solution
E.g the protein in the egg “albumin” once we put it in “heat” it will
be denatured and become insoluble.
Protein Misfolding
● Every protein must fold to achieve it’s normal conformation and
function
● Abnormal folding of proteins leads to a number of diseases in
human, e.g. Alzheimer’s and prion diseases
Alzheimer’s disease Creutzfeldt-Jacob (prion) disease
Prion protein is present in normal
brain tissues.
β amyloid protein is a misfolded
In diseases brains, the same
protein.
protein is misfolded.
It forms fibrous deposits or
Therefore it forms insoluble
plaques in the brain
fibrous aggregates that damage
brain cells.
Summary
Take Home Messages
- Native conformation of the protein: functional, fully folded structure.
- Unique 3D structure of native conformation is determined by primary
structure (amino acid sequence)
- Interactions between amino acids side-chains guide the folding of the
polypeptide chain to form secondary, tertiary, and sometimes
quaternary structures that cooperate in stabilizing the native
conformation of the protein.
- Protein denaturation results in unfolding and disorganization of the
protein’s structure, which aren’t accompanied by hydrolysis of peptide
bonds.
- Diseases can occur when an apparently normal protein assumes a
conformation that is cytotoxic, as in the case of Alzheimer’s or Prion’s
disease.
Question 1
there are .. different types of
amino acids?
A 9 C 11
B 10 D 20
Question 1
there are .. different types of
amino acids?
A 9 C 11
B 10 D 20
Question 2
2 peptide
A Bonds
Tripeptide
3 peptide
has ..? B Bonds
4 peptide
C Bonds
Question 2
2 peptide
A Bonds
Tripeptide
3 peptide
has ..? B Bonds
4 peptide
C Bonds
Question 3
The amino acid with a free amino
group is Called carboxyl terminus?
True False
Question 3
The amino acid with a free amino
group is Called carboxyl terminus?
True False
Question 4
Two or more polypeptide chains
make hydrogen bonding with each
other?
True False
Question 4
Two or more polypeptide chains
make hydrogen bonding with each
other?
True False
Biochemistry Team
Alanoud
Yasser Almutairi Lura Almusaeeb
Alnajawi
Ahmad Addas Hossam Alhussain Ghala Alyousef Shaden Alotaibi
Faisal Alomran Abdullah Alzoom Huda Bassam Aljawharah Alyahya
Abdulrahman Almalki Ziyad Alenazi Manar Alqahtani Norah Albahdal
Ziyad Bukhari Tariq Alshumrani Marwa Fal Ghaida Alotaibi
Talal Alrobaian Mohammed Almurshid Jenan Al-Sayari Ghida Alkahtani
Essam Nawaf Abdullah Almutlaq Rahaf Aldawood Lama Alhayan
Team Med444 Mays Altokhais Shaden Alshammari
