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Proteins
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Proteins, from the Greek proteios, meaning first, are a class of
organic compounds which are present in and vital to every living
cell.
In the form of skin, hair, callus, cartilage, muscles, tendons and
ligaments, proteins hold together, protect, and provide structure
to the body of a multicelled organism.
In the form of enzymes, hormones, antibodies, and globulins,
they catalyze, regulate, and protect the body chemistry.
In the form of hemoglobin, myoglobin and various lipoproteins,
they effect the transport of oxygen and other substances within
an organism.
Proteins
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Despite the variety of their physiological
function and differences in physical
properties--silk is a flexible fiber, horn a tough
rigid solid, and the enzyme pepsin water
soluble crystals--proteins are sufficiently
similar in molecular structure to warrant
treating them as a single chemical family.
Types of Proteins
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Fibrous Proteins As the name implies, these substances have fibrelike structures, and serve as the chief structural material in various
tissues.
Corresponding to this structural function, they are relatively insoluble in
water and unaffected by moderate changes in temperature and pH.
Subgroups within this category include:
Collagens & Elastins, the proteins of connective tissues. tendons
and ligaments.
Keratins, proteins that are major components of skin, hair, feathers
and horn.
Fibrin, a protein formed when blood clots.
Globular Proteins Members of this class serve regulatory,
maintenance and catalytic roles in living organisms.
They include hormones, antibodies and enzymes. and either dissolve or
form colloidal suspensions in water.
Such proteins are generally more sensitive to temperature and pH
change than their fibrous counterparts
Composition of Proteins
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Hydrolysis of proteins by boiling aqueous
acid or base yields an assortment of small
molecules identified as α-aminocarboxylic
acids.
More than twenty such components have
been isolated.
Essential amino acids diet components,
since they are not synthesized by human
metabolic processes.
Naturally Occuring Amino
Acids
Formation of Peptide Bond
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Amino acids are joined together in proteins by peptide bonds.
A peptide bond forms between the carboxyl group of one amino acid
(amino acid 1 in the figure below) and the amino group of the adjacent
amino acid (amino acid 2).
Amino Acid
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The basic building block of a protein is the amino acid.
Components of an amino acid
Each amino acid has at least one amine and one acid
functional group
Peptides and polypeptides
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Glycine and alanine can combine together
with the elimination of a molecule of water to
produce a dipeptide. It is possible for this to
happen in one of two different ways - so you
might get two different dipeptides.
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In each case, the linkage shown in blue in the
structure of the dipeptide is known as a
peptide link.
Peptides
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The linkage shown in blue in the structure of
the dipeptide is known as a peptide link.
If you joined three amino acids together, you
would get a tripeptide.
If you joined lots and lots together (as in a
protein chain), you get a polypeptide
A protein chain will have somewhere in
the range of 50 to 2000 amino acid
residues.
Naming a Peptide
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By convention, when you are drawing peptide
chains, the -NH2 group which hasn't been
converted into a peptide link is written at the
left-hand end. The unchanged -COOH group
is written at the right-hand end.
The end of the peptide chain with the -NH2
group is known as the N-terminal, and the
end with the -COOH group is the C-terminal.
Protein
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The end of the peptide chain with the -NH2 group is known as the Nterminal, and the end with the -COOH group is the C-terminal.
A protein chain (with the N-terminal on the left) will therefore look like
this:
Different Levels of Protein Structure
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Proteins fold in three dimensions. Protein
structure is organized hierarchically from socalled primary structure to quaternary
structure. Higher-level structures are motifs
and domains.
Primary Structure
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The primary structure is the sequence of amino acids in the
polypedptide chain.
Secondary Structure
Secondary structure is a local regulary
occuring structure in proteins and is mainly
formed through hydrogen bonds between
backbone atoms.
Alpha-helix
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Alpha helix is spiral
structure consisting
of tightly packed,
coiled backbone core
with side chains of
amino acids
extending outwards.
Beta-sheets
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Beta sheets are pleated
structures
Two or more
polypeptide chains
Can be parallel or
antiparallel
Tertiary structure
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Tertiary structure describes
the packing of alpha-helices,
beta-sheets and random coils
with respect to each other on
the level of one whole
polypeptide chain. Figure
shows the tertiary structure of
Chain B of Protein Kinase C
Interacting Protein
Quaternary structure
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Quaternary structure only
exists, if there is more than
one polypeptide chain present
in a complex protein. Then
quaternary structure describes
the spatial organization of the
chains. Figure shows both,
Chain A and Chain B of Protein
Kinase C Interacting Protein
forming the quaternary
structure.
Comparision of different levels of Protein
Structure
Protein Structure - Compared
Supersecondary structures
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A motif in this sense refers to a small specific combination of secondary
structural elements.
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Intermediate to secondary and tertiary structure.
They are stable arrangements of several arrangements of several
elements of secondary structure and connections between them.
The simplest motif with a specific function consists of two alpha-helices
joined by a loop region. Two such motifs are (i) a motif specific for DNA
binding and (ii)a motif specific for calcium binding
Supersecondary structures
form Supersecondary Motifs
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In many globular proteins, the secondary
structural motifs of α-helix or β-pleated sheet
forming supersecondary motifs.
β-α-β Unit
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Parallel beta-strands are connected by longer regions of chain which
cross the beta-sheet and frequently contain alpha-helical segments.
This motif is called the beta-alpha-beta motif and is found in most
proteins that have a parallel beta-sheet.
All three elements of secondary structure interact forming a
hydrophobic core.
β-Meander
Helix-turn-helix
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The loop regions connecting alpha-helical
segments can have important functions. For
example, in parvalbumin there is helix-turnhelix motif which appears three times in the
structure. Two of these motifs are involved in
binding calcium by virtue of carboxyl side
chains and main chain carbonyl groups. This
motif has been called the EF hand as one is
located between the E and F helices of
parvalbumin. It now appears to be a
ubiquitous calcium binding motif present in
several other calcium-sensing proteins such
as calmodulin and troponin C.
Helix-turn-helix
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Other examples include the
helix-turn-helix domain of
bacterial proteins that
regulate transcription and
the leucine zipper, helixloop-helix and zinc finger
domains of eukaryotic
transcriptional regulators.
Domains
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Different regions along a single polypeptide
chain can act as independent units, to the
extent that they can be excised from the
chain, and still be shown to fold correctly, and
often still exhibit biological activity. These
independent regions are termed domains.
Domains
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Domains sometimes act completely independently of
each other, as in the case of a catalytic domain and a
binding domain, where the two domains don't interact
with each other, but their association is synergistically
because the linker between them means that the
catalytic domain is kept in close contact to its
substrate.
In this case, the interaction between the domains
should be considered as something akin to quaternary
structure, rather that treating the whole complex as a
single protein.
Functions of Domain
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The tertiary structure of many proteins is built from
several domains.
Often each domain has a separate function to
perform for the protein, such as:
binding a small ligand (e.g., a peptide in the
molecule shown here)
spanning the plasma membrane (transmembrane
proteins)
containing the catalytic site (enzymes)
DNA-binding (in transcription factors)
providing a surface to bind specifically to another
protein.
Functions of Domain
Transmembrane proteins
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The polypeptide chain actually traverses the lipid bilayer. The figure
shows a transmembrane protein that passes just once through the
bilayer and another that passes through it 7 times. All G-protein
receptors (e.g., receptors of peptide hormones)