Download Basic Structure of Proteins

Basic Structure of
Proteins
Primary, Secondary, Tertiary &
Quaternary Structure of
Proteins
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THINGS YOU MUST KNOW
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How many structures does a protein have?
What is the primary structure of protein?
Which is the biological importance of the primary structure of proteins?
Which is the stabilizing chemical bond of primary structure of proteins?
What is the secondary structure of proteins?
Which is the stabilizing chemical bond of secondary structure of proteins?
List the different types of models of secondary structure of proteins
Describe the a-helix model
Describe the b-pleated sheet model
Describe the b-turn model
List the analogies and differences between a-helix and b-pleated sheet
structures
What is the tertiary structure of protein?
Which are the stabilizing chemical bonds of tertiary structure of proteins?
What is the importance of the tertiary level on protein structural
organization?
What is the quaternary structure of proteins?
Which are the stabilizing chemical bonds of quaternary structure of
proteins?
What is the importance of quaternary structure of proteins?
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• Proteins play a key role in biological processes. They can fulfill a vast variety
of tasks.
• Enzymes catalyze the complex set of chemical reactions that are
collectively referred to as life. These chemical reactions are on the other
hand regulated by proteins, which act either directly as components of
enzymes or indirectly in the form of chemical messengers, or their receptors.
• Proteins are engaged in the transport and storage of biologically
important substances such as metal ions, oxygene, glucose, lipids, and
many other molecules.
• In the form of muscle fibers and other contractile assemblies, proteins
generate the coordinated mechanical motion of numerous biological
processes, including the separation of chromosomes during cell
division and the movement of your eyes as you read this text.
• Proteins such as rhodopsin in the retina of your eye, acquire sensory
information that is processed through the action of nerve cell proteins.
• The proteins of the immune system, such as the immunoglobulins,
form an essential biological defense system in higher animals.
• Proteins carry out a wide range of functions in the cell. This variety in
capability is the result of the range of structures found in proteins and the
wide variety of molecules proteins can bind with high specificity.
• All of this results from the peculiar structure of proteins
• Protein function can be understood only in
terms of proteins structure. That means the
structure of a protein determines its
biochemical function.
• Amino Acid Sequence Determines Primary
Structure
• When the number, structure, and order of all of
the amino acid residues in a polypeptide are
known, its primary structure has been
determined.
• This is the subject of this lecture.
• In order to identify and classify known
and new protein structures it has been
found useful to describe the structure
of a protein in terms of four levels.
• Primary structure is the linear sequence of amino acids in the
polypeptide chain(s) of a protein.
• Secondary structure- the local spatial arrangement of a
polypeptides backbone atoms without regard to the
conformations of its side chains.
Secondary Structure consists of local regions of poly
peptide chains that have a regular conformation (helices, - sheets etc) which is stabilized by H-bonds.
• Tertiary structure - the overall arrangement of secondary
structure elements.
• Tertiary Structure refers to the 3-D configuration of an entire
polypeptide chain .This includes - helices & - sheets and
regions that are globular or spherical
• Quaternary structure- the arrangement of several
polypeptide chains
• Quaternary Structure consists of number of polypeptide chains
or subunits joined by noncovalent interactions.
4 organizational levels: primary, secondary, tertiary and
quaternary
Primary Structure of
Proteins
PRIMARY LEVEL OF PROTEIN
STRUCTURAL ORGANIZATION
It’s the sequence of amino acids linked
through peptide bonds
(Covalent backbone of the protein)
H2N-Glu-Ala-Val-Ser-Leu-Ala-Lys-Cys-COOH
H2N-Ala-Glu-Val-Ser-Ala-Leu-Lys-Cys-COOH
Primary Structure of Proteins
The particular sequence of amino acids
that is the backbone of a peptide chain or
protein
CH3
CH3
CH3 O
+
S
CH CH3
SH
CH2
CH O
CH2 O
CH2 O
-
H3N CH C N CH C N CH C N CH C O
H
H
Ala-Leu-Cys-Met
H
The particular sequence of amino acids in a
peptide or protein is referred to as the primary
structure. For example, a hormone that
stimulates the thyroid to release thyroxine
consists of a tripeptide Glu-His-Pro.
Although other sequences are possible for these three amino acids, only
the tripeptide with the Glu-His-Pro sequence of amino acids has hormonal
activity. Sequences such as His-Pro-Glu or Pro-His-Glu do not produce
hormonal activity. Thus the biological function of peptides as well as
proteins depends on the order of the amino acids.
When cells are damaged, a polypeptide called bradykinin is released at
the site,
which stimulates the release of prostaglandins. The presence of
bradykinin, which
contains nine amino acids, regulates blood pressure.
• Primary structure - the amino acid sequence of the proteins
polypeptide chains.
• Proteins are linear polymers of 20 different amino acids linked by covalent
amide bonds, called peptide bonds in a specific sequence of its constituent
amino acids.
• The sequence of amino acids that make up a protein is called its primary
structure.
• The Primary structure defines the linear sequence of amino acids and is due
to the peptide bond . The order of the amino acids is called the amino acid
sequence. The sequences of all polypeptide chains of a protein is defined as
the primary structure.
• The primary structure of a protein determines the three-dimensional
structure and the function of the protein.
• Peptide bonds are formed between the carbon atom (C) of the carboxyl
group and the nitrogen atom (N) of the amino group of an amino acid.
• Another way of saying this is that peptide bonds are formed by a
condensation reaction between the amine group of one amino acid and
the carboxyl group of another resulting in an amide group. The
elements of water are removed as a by product of this reaction. Water
(HOH) forms from the -OH of the carboxyl group of one amino acid and a
hydrogen from the -NH2 group of the other amino acid. The product is called
a peptide. Thus both peptides and proteins have amino and carboxyl ends.
• The amino acids can be linked in any order, but the order
of amino acids is unique to a given protein and is referred
to as that protein's "primary structure."
• The repeating sequence of “C-N-C-C-" resulting from
amide bond formation is called the "polypeptide
backbone."
• The directionality of the linkage results in directionality in the
resulting polypeptide chain. The amino group on the first amino
acid is referred to as the protein's "N-terminus" and the
carboxyl group on the last amino acid is the "C-terminus."
• Remember:
• Primary structure COVALENT PEPTIDE BONDS
• The protein backbone is represented as "C-N-C-C-".
• Peptide bonds are formed between the carbon atom (C) of the
carboxyl group and the nitrogen atom (N) of the amino group of
an amino acid
• The structure of a protein determines its biochemical function
• The amino acids can be linked in any order but the order of
amino acids is unique to a given protein and is referred to as
that protein's "primary structure."
SECONDARY LEVEL OF PROTEIN
STRUCTURAL ORGANIZATION
It’s the spatial arrangement of amino
acids inside the peptide chain stabilized
through hydrogen bonds between the
elements of the peptide bond.
(Interactions of neighboring amino acids)
Secondary Protein Structure
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Polypeptides form regular arrangements of amino acids called secondary structure
• The secondary structure of a protein is the local spatial arrangement of
a polypeptides backbone atoms without regard to the conformations of
its side chains.
• The secondary structure of a protein describes the way the amino
acids next to or near to each other along the polypeptide are arranged
in space.
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In order for proteins to fold into their characteristic three-dimensional "conformations" the
protein's "secondary structure" is adopted by hydrogen bonding between the N-H and
C=O groups along the backbone or primary structure of the protein.
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The three most common types of secondary structure are the alpha helix, the
beta-pleated sheet (parallel or anti-parallel), and the triple helix found in collagen.
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These patterns result from regular hydrogen bond patterns of backbone atoms in which the
polypeptide chain spirals around a central "helix axis" with a clockwise twist. Thus the
secondary structure of proteins refers to regular, repeated patters of folding of the protein
backbone to create the distinctive structures shared by many proteins.
In each type of secondary structure, we will look at the hydrogen
bonding between the hydrogen atom of an amino group in the
polypeptide chain and the oxygen atom of the carboxyl group in
another part of the chain.
• α-Helix
• Most common secondary structure.
• Three-dimensional arrangement of amino acids with the polypeptide
chain in a corkscrew shape or spiral . Looks like a coiled “telephone
cord”
• The a helix is a rodlike structure. The tightly coiled polypeptide main chain
forms the inner part of the rod, and the side chains extend outward in a
helical array off the long axis as shown in the slides that follow.
• The a helix is held together and stabilized by hydrogen bonds between the
NH and CO groups of the main chain. The CO group of each amino acid is
hydrogen bonded to the NH group of the amino acid that is situated four
residues ahead in the linear sequence in the next turn of the helix
• To repeat H bonds are formed between the H of –N-H group of one
amino acid and the –O of C=O of the fourth amino acid along the chain
• Because many hydrogen bonds form along the peptide backbone, this
portion of the protein takes the shape of a strong, tight coil that looks like a
telephone cord.
• All the side chains (R groups) of the amino acids are located on the outside
of the helix.
• α-Helix is found in
• Keratins – almost completely helical; major component of
hair, skin
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Rigidity determined by no. of –S-S- bonds
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Hb – 80% helical so globular, flexible molecule
• In the alpha helix, all the main-chain CO and NH groups are hydrogen
bonded. Each residue is related to the next one by a translation of 1.5 A
along the helix axis and a rotation of 100 degrees, which gives 3.6 amino
acid residues per turn of helix.
• Thus, amino acids spaced three and four apart in the linear sequence are
spatially quite close to one another in an a helix.
• In contrast, amino acids two apart in the linear sequence are situated on
opposite sides of the helix and so are unlikely to make contact.
• The pitch of the a helix is 5.4 A, the product of the translation (1.5 A) and the
number of residues per turn (3.6).
• The screw-sense of a helix can be right-handed (clockwise) or left-handed
(counterclockwise); the a helices found in proteins are right-handed.
• The a-helix content of proteins of known three-dimensional structure is
highly variable. In some, such as myoglobin and hemoglobin, the a
helix is the major structural motif.
• Other proteins, such as the digestive enzyme chymotrypsin, are virtually
devoid of a helix. The single-stranded a helix is usually a rather short rod,
typically less than 40 A in length.
• A variation of the a-helical theme is used to construct much longer
rods, extending to 1000 A or more. Two or more a helices can entwine
around each other to form a cable. Such a-helical coiled coils are found
in several proteins: keratin in hair, myosin and tropomyosin in muscle,
epidermin in skin, and fibrin in blood clots. The helical cables in these
proteins serve a mechanical role in forming stiff bundles of fibers.
Secondary structure includes various types of
local conformations in which the atoms of the
side chains are not involved.
• An -helix is generated when each carbonyl of a peptide bond forms a
hydrogen bond with the -NH of a peptide bond four amino acid
residues further along the chain.
– The side chains of the amino acid residues extend outward from the central
axis of the rod-like structure.
– The -helix is disrupted by proline residues, in which the ring imposed
geometric constraints, and by regions in which numerous amino acid
residues have charged groups or large, bulky side chains.
-HELIX
It’s the secondary level of protein
organization in which the polypeptide
backbone is tightly wound around an
imaginary axis as an spiral structure.
(Helicoidal arrangement of the peptide
chain)
CHARACTERISTICS OF HELIX
It is a rod-like structure
The polypeptide chain is folded into a helix
around a common axis
Amino terminus
There are about 3,6 amino acid residues per
turn of the helix
Each residue is linked to residues in the
preceding and following turns by hydrogen
bonds between the N-H groups and the oxygen
atom of the C=O group
Each amino acid establishes a hydrogen bond
with other situated 4 residues ahead the helix
The side chains R of the different residues
project radially from the helix
Carboxyl terminus
TYPES OF -HELIX
Left-handed
Right -handed
Right-handed -helix is much more
stable than left handed -helix
Essentially all -helix found in
proteins are right-handed
Secondary Structure – Beta
Pleated Sheet
• Another important periodic structural motif, or type of
secondary structure is known as the beta-pleated sheet.
• In a beta-pleated sheet, polypeptide chains are held
together side by side by hydrogen bonds between the
peptide chains.
• For example, in a beta-pleated sheet of silk fibroin, the
small R groups of the prevalent amino acids, glycine,
alanine, and serine, extend above and below the sheet.
• This results in a series of /3-pleated sheets that can be
stacked close together. The hydrogen bonds holding the
/3-pleated sheets tightly in place account for the strength
and durability of fibrous proteins such as silk.
• Comparison of β-sheet with α-helix
The beta pleated sheet differs markedly from the a helix in that
it is a sheet rather than a rod.
• The polypeptide chain in the beta pleated sheet is almost fully
extended as shown in the slides to follow rather than being
tightly coiled as in the a helix.
• The axial distance between adjacent amino acids is 3.5 A, in
contrast with 1.5 A for the a helix.
• Another difference is that the beta pleated sheet is stabilized
by hydrogen bonds between NH and CO groups in different
polypeptide strands, whereas in the a helix the hydrogen
bonds are between NH and CO groups in the same
polypeptide chain.
• Adjacent strands in a beta pleated sheet can run in the
same direction (parallel beta sheet) or in opposite
directions (antiparallel beta sheet).
• H-bonds perpendicular to long axis
• β-sheets are composed of two or more polypeptide chains
or extended segments of thesame polypeptide
Secondary Structure – Beta
Pleated Sheet
• Polypeptide chains are arranged
side by side
• Hydrogen bonds form between
chains
• R groups of extend above and
below the sheet
• Typical of fibrous proteins such
as silk
Secondary structure includes various types of
local conformations in which the atoms of the
side chains are not involved.
• -Sheets are formed by hydrogen bonds between two
extended polypeptide chains or between two regions of a
single chain that folds back on itself.
– These interactions are between the carbonyl of one peptide bond
and the -NH of another.
– The chains may run in the same direction or in opposite directions.
-PLEATED SHEET
• It’s the secondary level of protein organization
in which the backbone of the peptide chain is
extended into a zigzag arrangement
resembling a series of pleats.
• Disposition of the peptide bonds in planes of
alternating slopes
CHARACTERISTICS OF
-PLEATED SHEET
It is an extended structure made with
different -strands
The planes of consecutive peptide bonds have
different slopes (alternating ascending and
descending direction)
The side chain of adjacent amino acids point in
opposite direction
Hydrogen bonds link one -strand with other
and are perpendicular to the long axis of the
sheet
TYPES OF -PLEATED SHEET
Antiparallel
Parallel
Antiparallel is more stable than parallel
Both models are found in proteins
In some proteins, the polypeptide chain consists of mostly the a-helix
secondary structure, whereas other proteins consist of mostly the /3-pleated
sheet structure. Another group of proteins have a mixture with some sections of
the polypeptide chain in a-helixes and other sections in the /3-pleated sheet
structure. The tendency to form a certain type of secondary structure depends
on the amino acids in a particular segment of the polypeptide chain. The amino
acids that tend to form an a- helix or beta-pleated sheet follow.
• Remember:
• Secondary structure is HYDROGEN BONDS
-- hydrogen bonding between the N-H and
C=O groups along the backbone or primary
structure of the protein.
• The two most common folding patterns in
secondary structure are the a-helix and the bsheet (parallel or anti-parallel)
TYPES OF SECONDARY
LEVEL
• Random disposition
• -helix
Right handed
Left handed
• -pleated sheet
Parallel
Antiparallel
• -turn
Secondary Structure – Triple Helix
• Three polypeptide chains
woven together
• Glycine, proline, hydroxy
proline and hydroxylysine
• H bonding between –OH
groups gives a strong
structure
• Typical of collagen, connective
tissue, skin, tendons, and
cartilage
Triple Helix
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Collagen is the most abundant protein; it makes up as much as one-third of all
the protein in vertebrates. It is found in connective tissue, blood vessels, skin,
tendons, ligaments, the cornea of the eye, and cartilage.
The strong structure of collagen is a result of three polypeptides woven together like
a braid to form a triple helix, as seen in the next slide.
Collagen has a high content of glycine (33%), proline (22%), alanine (12%), and
smaller amounts of hydroxyproline, and hydroxylysine. The hydroxy forms of proline
and lysine contain — OH groups that form hydrogen bonds across the peptide chains
and give strength to the collagen triple helix. When several triple helixes wrap
together, they form the fibrils that make up connective tissues and tendons.
When a diet is deficient in vitamin C, collagen fibrils are weakened because the
enzymes needed to form hydroxyproline and hydroxylysine require vitamin C.
With out the — OH groups of hydroxyproline and hydroxylysine, there is less
hydrogen bonding between collagen fibrils.
Sores appear on the skin and gums, and blood vessels may be weakened, which
can lead to aneurisms and rupture. In a young person, collagen is elastic.
As a person ages, additional cross links form between the fibrils, which make
collagen less elastic.
Bones, cartilage, and tendons become more brittle, and wrinkles are seen as the skin
loses elasticity. In connective tissue disorders such as lupus and rheumatoid arthritis,
an over-active immune system produces increased amounts of collagen.
Organs in the body containing large amounts of connective tissues such as joints,
skin, kidneys, lungs, and heart are affected.
Hydrogen bonds between polar R groups in three polypeptide
chains form the triple helixes that combine to make fibers of
collagen.
Learning Check P1
Indicate the type of structure as
(1) primary
(2) alpha helix
(3) beta pleated sheet (4) triple helix
A.
B.
C.
D.
Polypeptide chain held side by side by H bonds
Sequence of amino acids in a polypeptide chain
Corkscrew shape with H bonds between amino
acids
Three peptide chains woven like a rope
Solution P1
Indicate the type of structure as
(1) primary
(2) alpha helix
(3) beta pleated sheet (4) triple helix
A.
B.
C.
D.
3 Polypeptide chain held side by side by H bonds
1 Sequence of amino acids in a polypeptide chain
2 Corkscrew shape with H bonds between amino
acids
4 Three peptide chains woven like a rope