Structure of proteins

• What is it that makes one protein an enzyme, another a

hormone, another a structural protein, and still another an
antibody? How do they differ chemically? The most obvious
distinctions are their structures.
• primary structure: sequence of amino acid residues.
• Secondary structure refers to particularly stable
arrangements of amino acid residues giving rise to
recurring structural patterns.
• Tertiary structure describes all aspects of the three-
dimensional folding of a polypeptide.
• quaternary structure :When a protein has two or more
polypeptide subunits, their arrangement in space is
referred to as quaternary structure.
Structures of proteins
 Primary structure
• Each type of protein has a unique amino acid
sequence. The sequences of amino acids is
primary structure.
• The function of a protein depends on its
amino acids sequence.
• Primary structure of a protein determines how
it folds up into its unique three-dimensional
structure, and this in turn determines the
function of the protein
 Amino acid sequences of millions of
proteins have been determined
• 1953: James D. Watson
and Francis Crick deduced
the double-helical
structure of DNA
• Frederick Sanger worked
out the sequence of
amino acid residues in the
polypeptide chains of the
hormone insulin.

• What determines the AA

sequences?
 Primary structure
• If the primary structure is altered, the function
of the protein may also change, giving rise to
genetic diseases. (sickle cell anemia)
• The altered properties of
hemoglobin S result from a
single amino acid
substitution, a Val instead of
a Glu residue at position 6 in
the two chains. The R group
of valine has no electric
charge, whereas glutamate
has a negative charge at pH
7.4. Hemoglobin S therefore
has two fewer negative
charges than hemoglobin A.
Hemoglobin become more
hydrophobic.
 Primary structure
• Proteins that have similar functions have
similar amino acid sequences in different
species. (The amino acid sequence of
ubiquitin is identical in species as disparate as
fruit flies and humans)

• Is the amino acid sequence absolutely fixed,

or invariant, for a particular protein?
 Primary structure
• No; some flexibility is possible. An estimated
20% to 30% of the proteins in humans are
polymorphic, having amino acid sequence
variants in the human population. Many of
these variations in sequence have little or no
effect on the function of the protein. E.g. vWF

• Conserved region
 Conformation
The spatial arrangement of atoms in a protein
is called its conformation.

Weak interaction, including hydrogen bond,

hydrophobic and ionic interaction, stabilize
the conformation of proteins.
In general, the protein conformation with the most
stable conformation is the one with the maximum
number of weak interactions
 Conformation
Most of the structural patterns reflect two
simple rules:
1. Hydrophobic residues are larges buried in the
protein interior, away from water.
2. The number of hydrogen bonds and ionic
interactions within the protein is maximized.
 The peptide bond is rigid and planar
• There is a resonance or partial sharing of two
pairs of electrons between the carbonyl
oxygen and the amide nitrogen.
• The peptide C⎯N bonds, because of their
partial double-bond character, cannot rotate
freely.
 The peptide bond is rigid and planar
• The six atoms of the peptide group lie in a
single plane, with the oxygen atom of the
carbonyl group trans to the hydrogen atom of
the amide nitrogen.
Planar of peptide group
 Summary: overview of structure
• Every protein has a three-dimensional
structure that reflects its function.
• Protein structure is stabilized by multiple weak
interactions. Hydrophobic interactions are the
major contributors to stabilizing the globular
form of most soluble proteins; hydrogen bonds
and ionic interactions are optimized in the
thermodynamically most stable structures.
 Secondary Structure
The term secondary structure refers to any
chosen segment of a polypeptide chain and
describes the local spatial arrangement of its
main-chain atoms, without regard to the
conformation of its side chains or its relationship
to other segments.
Common type: α helix, β conformation, β turn.
Secondary Structure: α helix
 Secondary Structure: α helix
1 Å(angstrom)=0.1nm ≈ length of C-N bond.
The polypeptide backbone is tightly wound
around an imaginary axis drawn longitudinally
through the middle of the helix, and the R
groups of the amino acid residues protrude
outward from the helical backbone.
Each repeating unit extends about 5.4Å along
the long axis. Each helical turn includes 3.6
amino acid residues
 Secondary Structure: α helix
About one-fourth
of all amino acid
residues in
proteins are found
in α helices

Most of the α
helix are right-
handed
 Secondary Structure: α helix
The structure is stabilized
by a hydrogen bond
between the hydrogen
atom attached to the
electronegative nitrogen
atom of a peptide linkage
and the electronegative
carbonyl oxygen atom of
the fourth amino acid on
the amino-terminal side of
that peptide bond
 Secondary Structure: α helix
• What is the length of a polypeptide with 80
amino acid residues in a single contiguous
helix?

• Each repeating unit extends about 5.4Å along

the long axis. Each helical turn includes 3.6
amino acid residues
 Secondary Structure: β Sheets
• The backbone:
zigzag structure.
• Hydrogen bonds
form between
adjacent
segments of
polypeptide
chain.
 Secondary Structure: β Sheets
• The R groups of
adjacent amino
acids protrude
from the zigzag
structure in
opposite
directions,
creating the
alternating
pattern
 Secondary Structure: β turns
• Gly and Pro residues often occur in β
turns, the former because it is small and
flexible, the latter because peptide bonds
involving the imino nitrogen of proline
readily assume the cis configuration , a
form that is particularly amenable to a
tight turn
Secondary Structure: β turns
 Summary: second structure
• Secondary structure is the local spatial
arrangement of the main-chain atoms in a
selected segment of a polypeptide chain.
• The most common regular secondary
structures are the helix, the conformation,
and turns.
Tertiary and Quaternary Structures
• Tertiary structure: the overall three-
dimensional arrangement of all atoms in a
protein. It includes longer-range aspects of
amino acid sequence.
• Quaternary structure: some proteins contain
several subunits. The arrangement of these
protein subunits in 3D complex constitutes
quaternary structure.
 Fibrous and globular proteins
• Fibrous proteins: polypeptide chains are
arranged in long strands or sheets. They
usually consist largely of a single type of
secondary structure.
• Globular proteins: polypeptide chains fold into
spherical or globular shape. More complex.
They are functional proteins.
 Fibrous proteins
• They are structural proteins, insoluble in water.
Fibrous proteins: keratin
 Fibrous proteins: Silk fibroin
• Produced by insects and spiders. Rich in Ala
and Gly residues. Mainly beta conformation.
Fibrous proteins: Silk fibroin
 Globular protein
• Structurally diverse and functionally diverse
 Summary: tertiary structures
• Tertiary structure is the complete three-
dimensional structure of a polypeptide chain.
There are two general classes of proteins based
on tertiary structure: fibrous and globular.
• Fibrous proteins, which serve mainly structural
roles, have simple repeating elements of
secondary structure.
• Globular proteins have more complicated tertiary
structures, often containing several types of
secondary structure in the same polypeptide
chain.