DIVERSITY OF STRUCTURES INCLUDED IN PROTEINS, PRODUCING A WIDE RANGE OF FUNCTIONS

Almost all living things’ dynamic function are protein dependent. As a matter of fact, protein’s
significance is underscored by their name, which was derived from the Greek word “proteios”, as “first”
or “primary” being its meaning. More than 50% of
the dry mass of most cells are obtained from protein
itself, and they serve very important purposes in
almost everything an organism does. Chemical
reactions can be boosted by some proteins, while
others play a role in defense, storage, transport,
cellular communication, movement, or structural
support.

It is impossible to create nor sustain life

without the presence of enzymes, which are greatly
composed of proteins. Metabolism is regulated by
enzymatic proteins by acting as catalyst, chemical
agents that selectively boost up chemical reactions without being depleted by the reaction. The fact that
enzyme can perform its function over and over again, we can consider it as workhorses that keeps cells
working by carrying out the process of life.

A human being can have tens of thousands of assortments of proteins, every single one
possessing a unique structure and functions; in point of fact, the most structurally sophisticated
molecules known are proteins. Constantly operates with distinctive functions, they extensively differ in
structure, each type of protein having a unique three-dimensional shape.

POLYPEPTIDES

Diverse in nature as proteins are, all of them are

unbranched polymers built up from the same set of 20 amino
acids. Polymers of amino acids are named as polypeptides.
Proteins are biologically functional molecules that consist of
one or more polypeptides, each folded and coiled into a
specific three-dimensional structure.

AMINO ACIDS MONOMERS

Common structure is being shared by all amino acids. An amino

acid is an organic molecule consist of both an amino group and a
carboxyl group (see figure 4.9). The illustration at the right displays the
general formula for an amino acid. An asymmetric carbon atom which
can be found at the center of the amino acid is called as alpha (a) carbon; it has four varieties of partners
named as the amino group, carboxyl group, hydrogen atom, and variable group symbolized by R. The R
group, or the side chain, is unique for each amino acid.

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What determines the unique characteristics of a particular amino acid is its physical and
chemical properties of the side chain, thus affecting its functional role in a polypeptide. As shown in
figure 5.16, amino acids are comprised based on the properties of their side chains One group is
composed of amino acids with non-polar side chains, which happens to be hydrophobic. Another group
composed of amino acids with polar side chains, which are hydrophilic. Acidic amino acids are those
with side chains that are mostly negative in charge owing to the existence of a carboxyl group., which
typically dissociated (ionized) at cellular pH. Basic amino acids have amino groups in their side chains
which are overall positive in charge. (Notice that all amino acids have carboxyl groups and amino groups;
the terms “acidic” and “basic” in this context is referring only to groups on the side chains. The fact that
they are charged makes acidic and basic side chains also hydrophilic.

AMINO ACIDS POLYMERS

After examining the amino acids, we can now see how linkages are formed to create polymers
(Figure 5,17). If two amino acids will be placed so that the carboxyl group of one is adjacent to the
amino group of the other, they can become
combined by a dehydration reaction, with the
elimination of a water molecule. The outcome
from the covalent bond is called a peptide bond.
Repeated constantly, this procedure yields a
polypeptide, a polymer of most numbers of
amino acids connected by peptide bonds.

Polypeptide backbone can be observed

by repeating the sequence of atoms as you can
see highlighted in purple in Figure 5.17.
Different side chains of (R groups) of the amino
acids are extending from this backbone. Polypeptides range in length from a few amino acids to a
thousand or more. A unique linear sequence can be observed in each specific polypeptide. Remember
that one end of the polypeptide chain possesses a free amino group, while the opposite end possesses a
free carboxyl group. Thus, a polypeptide of any length has one amino end (N Terminus) and one
carboxyl end (C Terminus). Looking at polypeptide’s inside of any significant size, you will observe the
side chains far outnumber the terminal groups. So as a whole, the chemical nature of the molecule is
determined by the kind and sequence of the side chains. The boundless sorts of polypeptides in nature
shows a significant concept introduced earlier- that many different polymers can be made by cells
through linking a limited set of monomers into diverse sequence.

PROTEIN STRUCTURE AND FUNCTION

Proteins’ specific activities result from their intricate three-dimensional architecture, the
simplest level of which is the sequence of their amino acids. Frederick Sanger, together with his
colleagues at Cambridge University in England, worked on the hormone insulin in the late 1940’s and
early 1950’s thus, making him the pioneer in
determining the amino acid sequence of
proteins. He used agents that collapses
polypeptides at specific places, followed by
chemical methods to determine the amino acid
sequence in these small fragments. After years
of effort, Sanger and his co-workers were able to
construct the complete amino acid sequence of
insulin. After that, most of the steps taken in
sequencing a polypeptide have been automated.

After discovering the sequence of the

amino acid of a polypeptide, what can it tell us
regarding the three-dimensional structure
(oftentimes referred to simple as the
“structure”) of the protein and its functions. The
term polypeptide and protein are not
synonymous to each other. Even considering the
fact that a protein consists of a single
polypeptide, somewhat, an analogous
relationship between a long strand of yarn and a
sweater of a particular size and shape that can
be from the yarn. A functional protein is not just
a polypeptide chain, but one or more
polypeptides precisely twisted, folded, and
coiled into a molecule of distinct shape (figure
5,18). And what determines the three-
dimensional structure the proteins will have
under normal cellular conditions is the amino
acid sequence of each polypeptide.

If a cell synthesizes a polypeptide, the chain folds spontaneously in a general manner, assuming
the functional structure for that protein. This particular act of folding is driven and reinforced by the
build up of variety of bonds between parts of the chain, which in turn depends on the sequence of the
amino acids. Numerous proteins are roughly spherical (globular proteins), while others are like long
fibers in shape (fibrous proteins). Even within these broad categories, countless variation exists.

A protein’s specific structure determines how It works. In almost every case, protein’s function is
merely depending on its ability to recognize and bind to some other molecule. In an especially striking
example of the marriage of form and function, see figure 5.19 shows the exact match of shape between
an antibody (a protein in the body) and the specific foreign substance on a flu virus that the antibody
sought to bind and destroy afterwards. In Chapter 43, we will be learning more about the way the
immune system produces antibodies that match the shapes of specific foreign molecules so swiftly. In
addition, we can also recall from Chapter 2 that natural signaling molecules called endorphins bind to a
specific receptor protein on the surface of brain cells in human beings, generating euphoria and eases
the pain. Morphine, heroin, and other opiate drugs have the capability to mimic endorphins for the
reason that they all share the similar shape with endorphins and can thus fit into and bind to endorphin
receptors for the brain. This particular fit is very exact, more of a lock and key (see figure 2.18). Thus,
protein’s function to exemplify, the ability of a receptor protein to bind to a specific pain-relieving
signaling molecule-will always be an emergent property resulting from exquisite molecular order.

FOUR LEVELS OF PROTEIN STRUCTURE

Having the objective to understand the

particular function of a protein, what’s
often productive is focusing on learning
about its structure. In spite of their huge
diversity, all proteins partake three
superimposed levels of structure, which is
being known as the primary, secondary,
and tertiary structure. A fourth level,
quaternary structure, arises when a
protein consists of two or more
polypeptide chains. Figure 5.20, on the
next two pages, shows and describes these
four levels of protein structure. Assure
yourself to study this figure thoroughly
before proceeding to the next section.
 EXPLORING LEVELS OF PROTEIN STRUCTURE

Protein’s primary structure is a linked series of

amino acids with a unique sequence. We can consider
transthyretin as an example, a globular blood protein
that transports vitamin A and one of the thyroid
hormones in the entire body system. Transthyretin is
composed of four identical polypeptide chains, each
composed of 127 amino acids. Being shown here is one
of these chains unraveled for a closer look at its primary
structure. Each of the 127 positions along the chain is
occupied by one of the 20 amino acids, indicated here
by its three-letter abbreviation.

The primary structure can be classified as the

order of letters in a very long word. If there will be a
chance, 20(127) different ways of making a polypeptide
chain 127 amino acids long may occur. Nonetheless, the
accurate primary structure of a protein is being
determined not by an irregular linking of the amino
acids, but by inherited genetic information. The main
structure in turn dictates secondary and tertiary
structure, due to the chemical nature of the backbone
and the side chains (R groups) of the amino acids placed
along the chain.

Most of the proteins have segments of their

own polypeptide chains repeatedly coiled or folded in patterns that contribute to the protein’s overall
form or shape. Collectively referred, these coils and folds are secondary structure, and are the result of
hydrogen bonds between the repeating constituents of the polypeptide backbone (not the amino acid
side chains). Inside the backbone, partial negative charge is infused into oxygen atoms, and the
hydrogen atoms attached to the nitrogen have a partial positive charge; as a result, hydrogen bonds can
form between these atoms. These hydrogen bonds are weak individually, however, their constant
repetition over a relatively long region of the polypeptide chain, they are able to support a particular
shape for that part of the protein.

One such secondary structure is the “a helix”, a delicate coil held together by hydrogen bonding
between every fourth amino acid as being shown. Although each transthyretin polypeptide has only one
a helix region, other globular proteins possess multiple stretches of “a helix” separated by nonhelical
regions. Some fibrous proteins, such as “a keratin”, hair’s structural protein have the “a helix) formation
over most of their length.
 There is another main type of secondary structure and it is called
as “B Pleated Sheet”. In this structure, two or more strands of the
polypeptide chain lying side by side (called b strands) are linked by
hydrogen bonds between parts of the two parallel polypeptide
backbones. B pleated sheets forms the core of numerous globular
proteins, including the case of transthyretin as an example, and
dominate some fibrous proteins, including the silk protein of a spider’s web. Each fiber silk is
stronger than a steel strand of the same weight because of the teamwork of so many hydrogen bonds.

Superimposed on the patterns of secondary structure is the tertiary structure of a protein, being
shown in a ribbon model of the transthyretin polypeptide. While secondary structure involves
connections and interactions between backbone constituents, tertiary structure is the overall shape of a
polypeptide resulting from interactions between the side chains (R group) of the different amino acids.
One specific type of interaction that contributes to tertiary structure is -somewhat misleadingly- called
the hydrophobic interaction. As polypeptide folds into its functional shape, amino acids with
hydrophobic (nonpolar) side chains typically end up in clusters at the center of the protein, having no
contact with water. Thus, a “hydrophobic interaction” is actually caused by the exclusion of nonpolar
substances by water molecules. Once nonpolar amino acid side chains are linked close together, van der
Waals interactions help hold them together. Meanwhile, hydrogen bonds between polar side chains and
ionic bonds between positively and negatively charged side chains also contributes in stabilizing tertiary
structure. There are all weak interactions in the aqueous cellular movement, however their cumulative
effect helps give the protein a distinct shape.

Covalent bonds called disulfide bridges may further reinforce the shape of a protein. Disulfide
bridges form where two cysteine monomers, which
have sulfhydryl groups (-SH) on their side chains are
brought close together by the constant folding of the
protein. The sulfur of one cysteine bonds to the sulfur
of the second, and the disulfide bridge(-S-S) rivets parts
of the protein together. All of these variety of
interactions can contribute to the tertiary structure of a
protein, as shown here in a small part of a hypothetical
protein.

Some proteins being composed of two or more polypeptide chains aggregated into one
functional macromolecule. Quaternary structure is defined as the overall protein structure that is being
generated from the aggregation of these polypeptide
subunits. For instance, shown is the complete globular
transthyretin protein, made up of its four
polypeptides.

Collagen can be defined as another example

which is a fibrous protein that has three identical
helical polypeptides intertwined into a larger triple
helix, providing the long fibers great strength. This
suits collagen fibers to their function as the girders of connective tissue in skin, bone, tendons,
ligaments, and other body parts. (Collagen accounts for 40% of the protein in the human body.)

The oxygen-binding protein of red blood cells is what

we call the Hemoglobin. It is another example of a globular
protein with quaternary structure. It is composed of four
polypeptide subunits, two of one kind (a) and two of
another kind (b). Both subunits consist primarily of a-helical
secondary structure. Each subunit has a non-polypeptide
component, called heme, with an iron atom that binds
oxygen.