The schedule of the lecture:

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The schedule of the lecture
The schedule of the lecture
Prepared by Iwona Katnik-Prastowska
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On the basis of the protein structure can be
distinquished
Globular proteins
Fibrilar proteins
and
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Globular proteins are so named, because their
polypeptide chains are folded into compact
structures, very unlike the extended, filamentous
forms of the fibrous proteins.
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Globular proteins form enormous class of
proteins. They are abundant and essential for
most of metabolic processes.
Some examples Myoglobin, hemoglobin,
Immunoglobulins, Cytokines, Albumin Transferrin
, Ceruloplasmin, Some peptide hormones, are
accounted to the class of globular proteins.
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Like all proteins, the globular proteins have
their individual three dimensional structure.
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Tertiary structure of globular proteins have
several outstanding features in common.
All proteins have a defined inside and outside.

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Side chain location varies with polarity The
amino acid side chains in globular proteins are
spatially distributed according to their
polarities
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The nonpolar residues Val, Leu, Ileu, Met,
Phe nearly always occur in the interior of a
protein, out of contact with the aqueous solvent.
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The charged polar residues Arg, His, Lys,
Asp, and Glu are almost invariably located on
the surface of a protein in contact with the
aqueous solvent.
Surfaces of globular proteins are coated by water
molecules.
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Uncharged polar Ser, Ther, Asn, Gln, Tyr, are
usually on the protein surface, but frequently
occur in the interior of the molecule and in
the latter case these residues are almost always
hydrogen bonded to other groups in the protein.
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The distribution of hydrophilic and hydrophobic
residues in globular proteins is characteristic
Green Hydrophilic aa
Red Hydrophobic aa
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Globular protein cores are efficiently arranged
and are quite compact there is very little
space inside them, so that water is largely
excluded from their interiors.
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Globular proteins are not static, but
continually undergo a wide variety of internal
motions, rapid fluctuations in its energy as a
consequence of interactions with the
environment.
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Large polypeptide chain is often locally folded
into globular clusters known as domains
Domains give these proteins multiglobal
appearance
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Domain is a portion of polypeptide chain that
folds on itself to form a compact unit that
remains recognizably distinct within the tertiary
structure of the whole protein Domains are
structurally independent units, each have the
characteristic of a small globular
protein. Domains often have a specific function
such as the binding of a small and larger
molecules.
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Immunoglobulin consist of independently folded,
globular regions-domains, connected in a modular
fashion
Each of domains show specific biological function.
The sequence of six immunoglobulin domains
differ, but all of the domains are folded
similarly.
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Fibronectin, an adhesive, multifunctional
glycoprotein with domains, which can specifically
bind to
cell
heparin
heparin
heparin
fibrin
collagen
fibrin
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Fibrous proteins
They are distinguished from globular proteins by
their filamentous or elongated form.

• Most of them play structural roles in animal
  cells and tissues
• They include the major proteins of
• skin,
• connective tissue,
• animal fibers like hair and silk.

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Fibrous proteins consist of particular kind,
mainly nonpolar amino acids
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The secondary structure of the fibrous proteins
can be predominantly
helical
pleated sheets
or unregular
or
In the fibrous proteins the helix is more expanded
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Collagens are structural proteins They are the
most abundant proteins in Vertebrates. It holds
the animal tissue together.

• Collagen fibers form the matrix
• material in bone, and cartillage,
• Important constituent of skin,
• Intercellular matrix,
• Connective tissue
• and dentine, on which the mineral constituents
  precipitate.

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Native collagen is a relatively insoluble
fibrous protein.
Denaturation
Collagen
Gelatin
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The most prominent amino acid of collagen is
Gly 33, Pro-Hyp 22, and Ala 11.
Collagen contains hydroxylysine, which rarely,
if ever, occurs in proteins.
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Tropocollagen
The basic unit of collagen is a tropocollagen
It consists of three helical polypeptide chains,
each having over 1000 aa residues.
The molecule of tropocollagen is stabilized by
forming hydrogen bonds.
Lenght 300 nm diameter 1,4 nm
Mol.mass 300 000 Daltons.
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The secondary structure of the collagen helix is
different from a-helix present in globular
proteins The left handed helical twisted, one
polypeptide chain is more expanded than a-helix
structure, and the collagen helix structure is
unique only to this protein.
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The structure of tropocollagen fibers
The secondary structure is helical on two
levels Each polypeptide has a left handed
helical sense, with 3,3 aa per turn and a total
linear distance of 9.6 Å per turn. Such 3
helical polypeptide chains are assembled into
tropocollagen cables consisting of 3 intertwisted
polypeptide chains, forming a superhelix with
right handed sense. Each turn consists of 36 aa.
Triple helix, Left handed
The structure is stabilized by hydrogen bonding
formed among the polypeptide chains.
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The superhelix of the tropocollagen
The superhelices are arranged in the superhelix
in a such way that the Gly are on the interior
and in the contact with each other.
Notice hydrogen bonding
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There is a gap between one end of one unit and
the start of another. These gaps play an
important role in bone and teeth formation. The
gaps in the quarter-stagger arrangement are
essential for the deposition of inorganic
crystals of calcium hydroxyapatite Ca3
(PO4)3OH. The gaps serve as the nucleation sites
for growth of these crystals. The combination
of hydroxyapatite crystals and collagen creates a
hard material that still has some springiness.
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Dentine, the main constituent of the internal
part of a tooth, contains a higher percentage
(75) of inorganic crystals, than does bone
and is therefore harder.
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Collagen undergoes extensive posttranslational
modification by
1.Translation on ribosomes
2.Hydroxylation of proline residues (require
Vit.C) and hydroxylation of lysine residues
3.Glycosylation to attach galactose 4.
Formation of triple helix 6. Removal of N- and
C-terminal domains 7. Oxidation and deamination
of lysine residues to form aldehyde (allysine)
and formation of crosslinks.
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Collagen fibrils are covalently cross-linked at
the ends of polypeptide chains. The following
amino acids are known to form such
linkage Lysine AlLysine Histidine 5-hydroxyllysin
e
Such a collagen infrastructure provides a final
product with tremendous amount of strength.
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The cross-linking process continues through life,
and the accumulating cross-links makes the
collagen steadily less elastic and more brittle.
As a result, bones and tendons in older
individuals are more easy snapped, and the skin
loses much of its elasticity.
Intensive cross-linking of polypeptide chains of
collagen have been associated with the aging
process.
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High dose of penicillamine, a metal chelator,
will also inhibit cross-linking and cause the
weakening of connective tissue.
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Microfibrils of tropocollagen can associate into
a fibril and several fibrils form the collagen
fiber.
Staggered arrangement of tropocollagen
In the native collagen individual tropocollagens
are assembled into microfibrils. Individual
tropocollagens interact laterally, so are aligned
in a linear head to tail fashion.
Each molecule is 300 nm long and overlaps its
neighbour by about 64 nm, producing charactristic
banded appearance of the fibers.
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There are over than 10 types of collagens I-XI
Collagens of different organs possess different
types of polypeptide chains. They differ from
each other on the basis of their amino acid
compositions and other properties like
carbohydrate content, types of chains,
cross-linking. However, each containing the same
motif of sequence Gly-Pro-Hyp
Collagen type I is most abundant in the human
organism. It accounts for about 90 of all
collagen.
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Extensive collagen degradation is seen in
Pagets disease, rheumatoid arthritis,
peridontal disease. In advanced disease Hyp is
often excreted in large amounts into the urine.
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Elastin is present in arterial blood vessels,
lungs, skin, nuchal ligament and form highly
elastic fibers
The polypeptide chain is rich in Gly, Ala, Val,
Lys, and contains desmosine. Lys is involved in
cross-links with desmosine.
Desmosine
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Fibroin is ß sheet fibrous protein, with a
polypeptide chain running parallel to the fiber
axis.
Fibroin is produced by silkworms and spiders.
Fibroin is ß sheet fibrous protein. Almost half
of its residues are glycines.
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The polypeptide chain of fibroin comprise
almost exclusively multiple repetition of the
sequence Gly-Ala-Gly-Ser-Gly-Ala-Ala-Gly-Ser
This allows the sheets to fit together and pack
on the top of one another. The arrangement
results in a fiber that is strong and relatively
inextensible.
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The keratins are predominantly a helical in
structure.
The a keratins are the major proteins of hair
and fingernails and compose a major fraction of
animal skin.
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Proposed structure for keratin-type intermediate
filaments
Monomer
In intermediate filaments, pairs of coiled
coils themselves tend to associate into a
four-chain protofilaments, and two of these in
turn pack together to form a protofibril, which
assoctiate to higher level.
Dimer
Protofilament
Protofibril
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Myosin and actin contractile proteins, that form
cytoskeletons of some cells and they elicit the
globular and fibrous structures
Myosin
Monomer of actin
Globular domain
Globular domen
Rodlike tail fibrous
Filament of actin
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