Structure of

Proteins
Text book
 Lesson Learning Outcomes
Students should be able to:
• Explain general features of amino acids.
• Categorize the amino acids.
• Understand zwitterion of amino acids.
• Describe different levels of protein.
• Compare protein folding with protein denaturation
• Describe nitrogen cycle, amino acid biosynthesis and
urea cycle.
 Amino Acids
Building Blocks of Proteins
 20 Common Amino Acids
Non-polar amino acids (9)
Polar, neutral/uncharged amino acids (6)
Polar, Acidic amino acids (2)
Polar, Basic amino acids (3)
• Biologically active proteins are polymers
consisting of amino acids linked by peptide
bonds
• A protein can be found in many conformations
• At least one or a few of these conformations
have biological activity  native conformation
Amino Acids Can Join Via Peptide Bonds
• Many proteins have no obvious regular
repeating structure
– described as having large segments of “random
structure” (random coil)
• Because proteins are complex, they are
defined in terms of four levels of structure
• Primary structure is the order in which the
amino acids are covalently linked together.
The peptide Leu—Gly—Thr—Val—Arg—Asp—
His (recall that the N-terminal amino acid is
listed first
• Secondary structure is the arrangement in
space of the atoms in the peptide backbone.
– The α-helix and β-pleated sheet arrangements
• Tertiary structure includes the three-
dimensional arrangement of all the atoms in
the protein, including those in the side chains
and in any prosthetic groups (groups of atoms
other than amino acids)
• A protein can consist of multiple polypeptide
chains called subunits. The arrangement of
subunits with respect to one another is the
quaternary structure
 Protein Structure
• Primary (1o) structure : the sequence of amino
acids in a polypeptide chain, read from the N-
terminal end to the C-terminal end
• The amino acid sequence (the primary
structure) of a protein determines its three-
dimensional structure
• striking demonstrations of the importance of
primary structure is found in the hemoglobin
associated with sickle-cell anemia
Secondary (2o) structure
• Cα—N (φ) and Cα—C (ψ)
bonds, are able to rotate
 Ramachandran angles
• conformation of a protein
backbone can be
described by specifying
the values of φ and ψ for
each residue (–180° to
180°)
• Secondary (2o) structure:
the ordered 3-dimensional
arrangements
(conformations) in localized
regions of a polypeptide
chain; refers only to
interactions of the peptide
backbone
– e. g., -helix and -pleated
sheet hydrogen bonded
structure
 α- helix
 Stabilized by hydrogen bond parallel to the
helix structure within the backbone of a single
polypeptide chain.
 Counting from the N-terminal, the C-O group
of each amino acid residue is hydrogen
bonded to the N-H group of amino acid four
residues away from it.
 Helical structure very stable.
• 3.6 residue in a turn of a helix
5.4 Å (0.54nm)
• Several factors can disrupt α-
helix:
– Amino acid proline creates a
bend in the backbone due to its
cyclic structure  cannot fit
into α-helix
Over-crowding by amino acid with
bulky R-side chain eg; valine,
isoleucine and threonine
 -Pleated Sheet
 polypeptide chains lie adjacent to one another;
may be parallel or anti-parallel
 R groups alternate, first above and then below
plane
 each peptide bond is s-trans and planar
 C=O and N-H groups of each peptide bond are
perpendicular to axis of the sheet
 C=O---H-N hydrogen bonds are between adjacent
sheets and perpendicular to the direction of the
sheet
Anti parallele β-pleated sheets
 -Helices and -Sheets
• Super secondary structures: the combination
of - and -sections, as for example
–  unit: two parallel strands of -sheet
connected by a stretch of -helix
–  unit: two antiparallel -helices (helix-turn-
helix)
– -meander: tight reverse turns form anti-parallel
sheets
– The Greek key: polypeptide chains double back
itself forming anti-parallel sheet
 Collagen triple helix

• Collagen, a component of bone and

connective tissue, is the most abundant
protein in vertebrates
• consists of three polypeptide chains wrapped
around each other in a rope-like twist, or
triple helix
• Each of the three chains has a
repeating sequence of three
amino acid residues, X—Pro—
Gly or X—Hyp—Gly, where Hyp
= hydroxyproline, and X = any
amino acid
– The triple helix is arranged so
that every third residue on each
chain is inside the helix.
– Only glycine is small enough to fit
into the space available
• Proline and hydroxyproline can constitute up
to 30% of the residues in collagen.
• Hydroxylysine also occurs in collagen.
• The three individual collagen chains are
themselves helices that differ from the α-helix
• They are twisted around each other in a
superhelical arrangement to form a stiff rod.
This triple helical molecule is called
tropocollagen
– 300 nm (3000 Å) long and 1.5 nm (15 Å) in
diameter.
– held together by hydrogen bonds involving the
hydroxyproline and hydroxylysine
• Tertiary (3°) structure:
• three dimensional shape of the polypeptide
• Forms spontaneously as a result of attractions and
repulsions between the various amino acids in the protein
 What Are the Noncovalent Interactions That
Dictate and Stabilize Protein Structures?

 van der Waals: 0.4 - 4 kJ/mol

 hydrogen bonds: 12-30 kJ/mol
 ionic bonds: 20 kJ/mol
 hydrophobic interactions: <40 kJ/mol
 Forces holding a tertiary protein
structure
• Backbone hydrogen bonding is a major
determinant of secondary structure
– hydrogen bonds between the side chains of amino
acids are also possible in proteins
• Nonpolar residues cluster together in the
interior of protein molecules  hydrophobic
interactions
• Electrostatic attraction occurs on the surface
of the molecule  groups being close to one
another
• disulfide bonds form covalent links between
the side chains of cysteines
• The three-dimensional conformation of a
protein is the result of the interplay of all the
stabilizing forces
Myoglobin: An Example of Protein
Structure
• a globular protein
• Complete myoglobin molecule consists is a
single polypeptide chain of 153 amino acid,
includes a prosthetic group, heme
• Myoglobin has eight α-helical regions and no
β-pleated sheet regions
• Hydrogen bonding in the polypeptide backbone
stabilizes the α-helical regions and side chains
• Quaternary (4°) structure: the association of
polypeptide chains into aggregations
• Consists of two or more polypeptide chains
• Proteins are divided into two large classes based on
their three-dimensional structure
– fibrous proteins
– globular proteins
• Each chain is called a subunit
• Number of chains can range from two to more
than a dozen
• dimers, trimers, and tetramers, consisting of
two, three, and four polypeptide chains,
respectively (oligomer.)
• As a result of these noncovalent interactions,
subtle changes in structure at one site on a
protein molecule may cause drastic changes in
properties at a distant site.
• Proteins that exhibit this property are called
allosteric.
 Fibrous Proteins
• Fibrous proteins: contain polypeptide chains
organized approximately parallel along a single
axis. They
– consist of long fibers or large sheets
– tend to be mechanically strong
– are insoluble in water and dilute salt solutions
– play important structural roles in nature
• Examples are
– keratin of hair and wool
– collagen of connective tissue of animals including cartilage,
bones, teeth, skin, and blood vessels
 Globular Proteins
• Globular proteins: proteins which are folded to
a more or less spherical shape
– they tend to be soluble in water and salt solutions
– most of their polar side chains are on the outside and
interact with the aqueous environment by hydrogen
bonding and ion-dipole interactions
– most of their nonpolar side chains are buried inside
– nearly all have substantial sections of -helix and -sheet
• Examples are
– myoglobin
– hemoglobin
 Denaturation
• Denaturation: the loss of the structural order (2°,
3°, 4°, or a combination of these) that gives a
protein its biological activity; that is, the loss of
biological activity
• Denaturation can be brought about by
– heat
– large changes in pH, which alter charges on side chains, e.g., -
COO- to -COOH or -NH2+ to -NH3
– detergents such as sodium dodecyl sulfate (SDS) which disrupt
hydrophobic interactions
– urea and guanidine hydrochloride, which disrupt hydrogen
bonding
– mercaptoethanol, which reduces disulfide bonds to two
sulfhydryl group
 Protein Folding Chaperones
 primary structure conveys all information necessary
to produce the correct 3° structure.
 nonetheless, in the protein-dense environment of a
cell, proteins may begin to fold incorrectly or may
associate with other proteins before folding is
completed.
 special proteins called chaperones aid in the correct
and timely folding of many proteins.
 hsp70 was the first protein chaperone discovered
 chaperones exist in organisms from prokaryotes to
humans.
 Protein folding vs Protein denaturation
➢ Protein folding: the folding of polypeptide into functional
3D structure.
▪ Proteins may begin to fold incorrectly or may associate
with other proteins before folding is completed.
▪ The incorrect protein folding is due to the hydrophobic
regions that should be buried inside the protein remain
exposed.

➢ Protein denaturation: the loss of the structural order (2°,

3°, 4°, or a combination of these) that gives a protein its
biological activity.
▪ Denaturation can be brought about by heat, pH, detergent
and urea.
 End
of lecture

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