Proteins

Protein structure
• Each protein in your cells consists of one or more
polypeptide chains.
• Each of these polypeptide chains is made up of amino acids,
linked together in a specific order.
• The structure and function of the polypeptide, and the
protein it's part of are determined by chemical properties of
and order of the amino acids.
Protein structure
• The shape of a protein is very important to its function.
• There are four levels of protein structure: primary,
secondary, tertiary, and quaternary.
Primary structure

• The simplest level of protein structure, primary structure, is

simply the sequence of amino acids in a polypeptide chain.
• For example, the hormone insulin has two polypeptide
chains, A and B.
• In insulin, each chain has its own set of amino acids,
assembled in a particular order.
• The sequence of the A chain is different from the sequence
of the B chain.
Primary structure

• The sequence of a protein is determined by the DNA of the

gene that encodes the protein.
• A change in DNA sequence of the gene may lead to a change
in the amino acid sequence of the protein.
• Even changing just one amino acid in a protein’s sequence
can affect the protein’s overall structure and function.
Primary structure

• For example, a single amino acid change is associated with

sickle cell anemia.
• In sickle cell anemia, one of the polypeptide chains that
make up hemoglobin has a slight sequence change.
• The glutamic acid that is normally the sixth amino acid of the
hemoglobin β chain of hemoglobin is replaced by a valine.
Primary structure
Primary structure

• What’s remarkable about this?

A hemoglobin molecule is made up of two α chains and two β
chains, each consisting of about 150 amino acids.
The difference between a normal hemoglobin molecule and a
sickle cell molecule is just 2 amino acids out of the
approximately 600.
The glutamic acid-to-valine amino acid change makes the
hemoglobin molecules to assemble into long fibers.
A person whose body makes only sickle cell hemoglobin will
suffer symptoms of sickle cell anemia.
Figure 10: Normal
and fibrous
haemoglobin.

The amino acid

change (Glu → Val)
alters the
structure of
haemoglobin,
causing it to
form insoluble
fibrous strands
which cannot carry
oxygen as
effectively
Primary structure

• The fibers distort disc-shaped red blood cells into crescent shapes.
Primary structure

• The sickle-shaped cells do not carry as much oxygen and

therefore deliver less oxygen to the body’s tissues.
• These cells are also fragile and can break, causing painful
“crises” because they disrupt blood flow.
• The sickled cells get stuck as they try to pass through blood
vessels.
• The stuck cells impair blood flow and can cause serious
health problems for people with sickle cell anemia.
Secondary structure

• The next level of protein structure, secondary structure

• The secondary structure refers to local folded structures that
form within a polypeptide.
• The local folded structures are due to interactions between
atoms of the polypeptide backbone.
Secondary structure does not involve R group atoms.
Secondary structure
• The most common types of secondary structures are the α
helix and the β pleated sheet.
• Both structures are held in shape by hydrogen bonds, which
form between the carbonyl O of one amino acid and the
amino H of another.
Secondary structure

• In an α helix, the carbonyl (C=O) of one amino acid is

hydrogen bonded to the amino H (N-H) of an amino acid that
is fourth down the chain.
• This pattern of bonding pulls the polypeptide chain into a
helical structure.
Secondary structure

• The helical structure resembles a curled ribbon, with each

turn of the helix containing 3.6 amino acids.
• The R groups of the amino acids stick outward from the α
helix, where they are free to interact.
Secondary structure
• In a β pleated sheet,
two or more segments of a polypeptide chain line up next to
each other, forming a sheet-like structure held together by
hydrogen bonds.
The hydrogen bonds form between carbonyl and amino
groups of backbone.
The R groups extend above and below the plane of the sheet.
The strands of a β pleated sheet may be parallel or
antiparallel
Secondary structure
• Certain amino acids are more or less likely to be found in α-
helices or β pleated sheets.
• For instance, the amino acid proline is sometimes called a
“helix breaker” because its unusual R group bonds to the
amino group to form a ring.
• This creates a bend in the chain and is not compatible with
helix formation.
• Proline is typically found in bends (unstructured regions
between secondary structures).
Secondary structure
• Amino acids such as tryptophan, tyrosine, and
phenylalanine, (with large ring structures in their R groups),
are often found in β pleated sheets.
Possible explanation-the β pleated sheet structure provides
plenty of space for the side chains.
Secondary structure
• Many proteins contain both α helices and β pleated sheets,
• Some contain just one type of secondary structure while
others do not form either type.
Tertiary structure
• The overall three-dimensional structure of a polypeptide is
called its tertiary structure.
• The tertiary structure is primarily due to interactions
between the R groups of the amino acids that make up the
protein.
Tertiary structure
• R group interactions that contribute to tertiary structure are
basically the whole range of non-covalent bonds.
• The interactions include:
Hydrogen bonding.
 Ionic bonding.
Dipole-dipole interactions.
 London dispersion forces (induced dipole-induced dipole attraction).
• In addition there is one special type of covalent bond that can
contribute to tertiary structure: the disulfide bond.
Tertiary structure

• R groups with like charges repel one another, while those

with opposite charges can form an ionic bond.
• Similarly, polar R groups can form hydrogen bonds and other
dipole-dipole interactions.
Tertiary structure
• Hydrophobic interactions are also important to tertiary
structure.
Amino acids with hydrophobic R groups cluster together on
the inside of the protein, leaving hydrophilic amino acids on
the outside to interact with surrounding water molecules.
Tertiary structure
• Disulfide bonds which are covalent linkages form between
the sulfur-containing side chains of cysteines.
• These are much stronger than the other types of bonds that
contribute to tertiary structure.
• Thus disulfide bonds can make a protein's tertiary structure
more resistant to denaturing influences like heat or salt.
• They act like molecular "safety pins," keeping parts of the
polypeptide firmly attached to one another.
Tertiary structure
Quaternary structure

• Many proteins are made up of a single polypeptide chain and

have only three levels of structure.
• However, some proteins are made up of multiple
polypeptide chains, also known as subunits.
• When these subunits come together, they give the protein
its quaternary structure.
Quaternary structure
• We’ve already encountered one example of a protein with
quaternary structure: hemoglobin.
As mentioned earlier, hemoglobin carries oxygen in the
blood and is made up of four subunits, two α and two β
types.
• Another example is DNA polymerase which is composed of
ten subunits.
Quaternary structure
• In general, the same types of interactions that contribute to
tertiary structure also hold the subunits together to give
quaternary structure.
• These are mostly weak interactions, such as hydrogen
bonding and London dispersion forces (Van der Waals forces)
Denaturation and protein
folding
• Each protein has its own unique shape.
• However changes in temperature or pH of a protein's
environment or exposure to chemicals may disrupt
intramolecular interactions.
• This causes the protein to lose its three-dimensional
structure and turn back into an unstructured string of amino
acids.
• When a protein loses its higher-order structure, but not its
primary sequence, it is said to be denatured.
Denaturation and protein
folding
• Denatured proteins are usually non-functional
• For some proteins, denaturation can be reversed if returned
to their normal environments.
• Other times, however, denaturation is permanent e.g., when
an egg is fried.
Denaturation and protein
folding
• Some proteins can re-fold after denaturation even when they
are isolated in a test tube.
• Since these proteins can go from unstructured to folded all
by themselves, their amino acid sequences must contain all
the information needed for folding.
• However, many proteins don’t fold by themselves, but
instead get assistance from chaperone proteins.
The end