STRUCTURES AND FUNCTIONS

OF PROTEIN

Ika Yustisia
Department of Biochemistry
Faculty of Medicine UNHAS
2017
 Definition

What is protein?
 Definition

J.J. Berzelius G. J. Mulder

The word protein that I propose to you . . . I would wish to

derive from proteios, because it appears to be the
primitive or principal substance of animal nutrition that
plants prepare for the herbivores, and which the latter
then furnish to the carnivores.
—J. J. Berzelius, letter to G. J. Mulder, 1838
 Definition
Proteins are
• The most abundant biological macromolecules
• Thousands of different kinds
• Ranging in size
• Exhibit enormous diversity of biological function
• Most important final products of the
information pathways
• The molecular instruments through which
genetic information is expressed
 Definition
Proteins are
polymers of
amino acids,
with each amino
acid residue
joined to its
neighbor by a
specific type of
covalent bond
Definition
PROTEINOGENIC AMINO ACIDS
PROTEINOGENIC AMINO ACIDS
PROTEINOGENIC AMINO ACIDS
NON-PROTEINOGENIC AMINO ACIDS
 Structure of Protein
The Four Orders of Protein Structure

Not all protein have a quartenary structure

 Structure of Protein
• 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 specific structures that are
thermodynamically most stable
 Structure of Protein
• Primary structure is the sequence of the
amino acids in a polypeptide chain
• Secondary structure is the regular
arrangement of amino acid residues in a
segment of a polypeptide chain, in which
each residue is spatially related to its
neighbors in the same way
 Structure of Protein

• Globular proteins have compact shapes. Most

are water soluble, but some are incorporated
into cellular membranes or into supramolecular
aggregates such as the ribosomes. Hemoglobin
and myoglobin, enzymes, membrane proteins,
and plasma proteins are globular proteins
 Structure of Protein

• Fibrous proteins are long and threadlike, and

most serve structural functions. The keratins of
hair, skin, and fingernails are fibrous proteins, as
are the collagen and elastin of the extracellular
matrix
 Structure of Protein
• 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
• Quaternary structure results from interactions between
the subunits of multisubunit (multimeric) proteins or
large protein assemblies
 Structure of Protein

Myoglobin

Hemoglobin
Structure of Protein

Insulin
 Structure of Protein
Protein Denaturation
• All proteins begin their existence on a ribosome
as a linear sequence of amino acid residues.
• This polypeptide must fold during and following
synthesis to take up its native conformation
• Modest changes in the protein’s environment
can bring about structural changes that can
affect function
 Structure of Protein
Protein Denaturation
• Protein structures have evolved to function in
particular cellular environments
• Conditions different from those in the cell can
result in protein structural changes, large and
small
• A loss of three-dimensional structure sufficient
to cause loss of function is called denaturation
 Structure of Protein
Protein Denaturation
• Three-dimensional structure of proteins
can be destroyed by heating, detergents,
nonpolar organic solvents, heavy metals,
and extreme pH.
• This process of denaturation leads to a
complete loss of the protein's biological
properties
 Structure of Protein

Protein Denaturation
• Organic solvents, urea, and detergents act
primarily by disrupting the hydrophobic
interactions that make up the stable core of
globular proteins
• Extremes of pH alter the net charge on the
protein, causing electrostatic repulsion and
the disruption of some hydrogen bonding
 Protein Function
• Proteins are the most versatile macromolecules
in living systems and serve crucial functions in
essentially all biological processes

Luciferin Hemoglobin Keratin

 Protein Function

• Proteins function as catalysts, they transport

and store other molecules such as oxygen, they
provide mechanical support and immune
protection, they generate movement, they
transmit nerve impulses, and they control
growth and differentiation
 Protein Function

What proteins do and

how they perform their
functions?
 Protein Function
Several key properties enable proteins to
participate in such a wide range of functions
• Proteins are linear polymers built of monomer
units called amino acids
• Proteins contain a wide range of functional
groups
• Proteins can interact with one another and with
other biological macromolecules to form
complex assemblies
 Protein Function

• Some proteins are quite rigid, whereas others

display limited flexibility
• Protein function often entails interactions with
other molecules
• A molecule bound by a protein is called a ligand,
and the site to which it binds is called the
binding site
 Plasma Proteins
• The concentration of total protein in human
plasma is approximately 7.0–7.5 g/dL and
comprises the major part of the solids of the
plasma. The proteins of the plasma are
actually a complex mixture that includes not
only simple proteins but also conjugated
proteins such as glycoproteins and various
types of lipoproteins
 Plasma Proteins
• Some 100 different
proteins occur in human
blood plasma
• Most plasma proteins are
synthesized in the liver
• Albumin (69 kDa) is the
major protein of human
plasma (3.4–4.7 g/dL)
and makes up ± 60% of
the total plasma protein
Plasma Proteins
Plasma Proteins
 Myoglobin & Hemoglobin
Reversible Binding of a Protein to a Ligand: Oxygen-Binding
Proteins
• Myoglobin (Mr 16,700; abbreviated Mb) facilitates oxygen
diffusion in muscle.
• Myoglobin is a single polypeptide of 153 amino acid residues
with one molecule of heme. It is typical of the family of
proteins called globins, all of which have similar primary
and tertiary structures. The polypeptide is made up of eight
-helical segments connected by bends
• About 78% of the amino acid residues in the protein are
found in these helices
 Myoglobin & Hemoglobin
Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins
• Hemoglobin (Mr 64,500; abbreviated Hb) is roughly spherical,
with a diameter of nearly 5.5 nm. It is a tetrameric protein
containing four heme prosthetic groups, one associated with
each polypeptide chain
• Adult hemoglobin contains two types of globin, two α chains (141
residues each) and two β chains (146 residues each)
• The polypeptide sequences of the α and β subunits are identical,
the three-dimensional structures of the two types of subunits are
very similar
• Their structures are very similar to that of myoglobin
Myoglobin & Hemoglobin
Myoglobin & Hemoglobin
 Myoglobin & Hemoglobin
Clinical correlation
CO poisoning – COHb
Carbon monoxide (CO), a colorless, odorless gas,
is responsible for more than half of yearly deaths
due to poisoning worldwide. CO has an
approximately 250-fold greater affinity for
hemoglobin than does oxygen. Consequently,
relatively low levels of CO can have substantial
and tragic effects.
 Myoglobin & Hemoglobin
Clinical correlation
Sickle cell anemia
A genetic disease caused by a single amino acid
substitution (Glu6 to Val6) in each chain of
hemoglobin. The change produces a
hydrophobic patch on the surface of the
hemoglobin that causes the molecules to
aggregate into bundles of fibers
 Myoglobin & Hemoglobin
Clinical correlation

Sickle cell anemia

 Immunoglobulins
Complementary Interactions between Proteins
and Ligands: Immunoglobulins
Soluble antigen receptors, which are formed by
activated B cells and released into the blood, are
known as antibodies, also known as
immunoglobulins
 Immunoglobulins

• Immunoglobulins contain a minimum of two

identical light (L) chains (23 kDa) and two
identical heavy (H) chains (53–75 kDa), held
together as a tetramer (L2H2) by disulfide
bonds
 Immunoglobulins

• Immunoglobulins contain a minimum of two

identical light (L) chains (23 kDa) and two
identical heavy (H) chains (53–75 kDa), held
together as a tetramer (L2H2) by disulfide
bonds
 Immunoglobulins
• Human immunoglobulins are divided into five
classes. IgA (with two subgroups), IgD, IgE, IgG
(with four subgroups), and IgM are defined by
their H chains, which are designated by the
Greek letters α, δ, ε, γ, and μ. By contrast,
there are only two types of L chain κ and λ
 Numbers Serum
Molecular Heavy Light
Ig weight
of Ig
chain chain
concentration % in serum
units (g/L)
Ig G 150.000 1 γ κλ 7-16 75
Ig A 160.000 1,2 α κλ 0,7-4 10-15
Ig M 900.000 5 μ κλ 0,4-2 5-10
Ig D 185.000 1 δ κλ <0,04 <1
Ig E 200.000 1 ε κλ <0,5 <1
 Actin and Myosin
The Major Proteins of Muscle Are Myosin and
Actin
• The contractile force of muscle is generated by
the interaction of two proteins, myosin and
actin. Together, these proteins make up more
than 80% of the protein mass of muscle.
 Actin and Myosin
The Major Proteins of Muscle Are Myosin and Actin
• Myosin (Mr 540,000) has six subunits: two heavy
chains (each of Mr 220,000) and four light chains
(each of Mr 20,000)
• At its amino terminus, each heavy chain has a
large globular domain containing a site where
ATP is hydrolyzed
• In muscle cells, molecules of myosin aggregate to
form structures called thick filaments These
rodlike structures serve as the core of the
contractile unit
 Actin and Myosin
The Major Proteins of Muscle Are Myosin and Actin
• Myosin (Mr 540,000) has six subunits: two heavy
chains (each of Mr 220,000) and four light chains
(each of Mr 20,000)
• At its amino terminus, each heavy chain has a
large globular domain containing a site where
ATP is hydrolyzed
• In muscle cells, molecules of myosin aggregate to
form structures called thick filaments These
rodlike structures serve as the core of the
contractile unit
Actin and Myosin
 Actin and Myosin
The Major Proteins of Muscle Are Myosin and
Actin
• Actin is abundant in almost all eukaryotic cells.
In muscle, molecules of monomeric actin,
called G-actin (globular actin; Mr 42,000),
associate to form a long polymer called F-actin
( filamentous actin)
• The thin filament consists of F-actin, along
with the proteins troponin and tropomyosin
 Actin and Myosin
The Major Proteins of Muscle Are Myosin and
Actin
• Other muscle proteins: α-actinin, desmin,
vimentin, nebulin, paramyosin, C-protein, M-
protein, titins
Signaling Substances and Hormones

Histidine

Tyrosine
Signaling Substances and Hormones
 REFERENCES
• Meisenberg, G., Simmons, WH. Principles of
Medical Biochemistry, 2 ed. Mosby Elsevier, 2006
• Koolman, J.; Roehm, KH. Color Atlas of
Biochemistry, 2 ed. Thieme, 2004
• Devlin, TM. Textbook of Biochemistry with Clinical
Correlations, 6th ed., Wiley Liss, 2006
• Murray, RK., et al. Harper’s Ilustrated Biochemistry,
28th ed., Lange Medical Books/McGraw-Hill, 2009
• Nelson, DL, Cox, MM. Lehninger Principles of
Biochemistry, 5th ed., WHFreeman, 2009