Levels of protein structure (let these notes and the class notes supplement each other).
1. Primary structure. This is the amino acid sequence. Amino acids (a.a.) are covalently bonded
(one to the next) via dehydration synthesis, involving the carboxyl group of one a.a and the
amino group of the next a.a. This covalent bond is often called a peptide bond, but it's still a
covalent bond. Small proteins might contain 30 - 50 a.a.; large ones can have some hundreds of
a.a. Note that the primary structure ultimately determines the higher levels of structure (i.e. how
a protein is folded into its final shape); if you change the a.a. sequence of the primary structure,
then the protein will fold up (tertiary structure) into a different shape. A change of even one
amino acid may be enough to change the 3-D structure of the protein and to cause it to
malfunction. That's the case in sickle cell anemia, where one small change in the amino acid
sequence of one of the two types of hemoglobin polypeptides creates a dramatically damaging
effect on the human body.
2. Secondary structure. Two kinds: (a) alpha helix, (b) beta pleated sheet. A given protein may
contain either one or both. (See text illustrations.) Both are stabilized by hydrogen bond
formation between the carbonyl (C=O) oxygen atom of one a.a. and the amino group's hydrogen
atom of another a.a. The H bonds form along the axis of the alpha helix, but they form side-toside in the pleated sheet, between stretches of the polypeptide lying side by side.
3. Tertiary structure. The very long molecule (many amino acids linked together; roughly like a
long string of beads) folds back upon itself to form an irregularly shaped (bumpy, knobby,
pitted), more or less compact molecule, something like a loosely closed fist. Folding forces
some stretches of the a.a. sequence toward the interior of the compacted molecule, whereas other
stretches of a.a. are exposed at the molecule's surface. This folding forces side chains of a.a. to
interact with each other within the folded molecule and to interact with the surrounding solvent
(remember that proteins typically are dissolved in water within organisms). So, the forces
responsible for maintaining this folded compact shape are:
a. hydrogen bonds. Some amino acid side chains contain functional groups that can form H
bonds with each other: amino, carboxyl, hydroxyl.
b. ionic interactions (= charge interactions, electrostatic interactions). Look for the a.a. that
have carboxyl or amino groups in their side chains. These may be charged at the solution's pH
and therefore capable of attracting (+/-) or repelling (+/+, -/-) each other when the protein folds
up.
c. disulfide bonds (the covalent bond in the disulfide group: S-S). This covalent bond can form
between the sulfhydryl (-SH) groups in the side chain of the a.a. called cysteine (see structure in
text). -SH + HS- → -S-S- A typical protein may have a few to several of these covalent
bonds.
d. hydrophobic interactions (the hydrophobic effect). This is based on the interaction of a.a.
side chains with the surrounding solvent, water. Remembering that the protein is usually
surrounded by water, the folded molecule will be more stable if: (i) hydrophobic a.a. side chains
are tucked away toward the interior of the folded protein as much as possible (i.e. away from the
water) and (ii) hydrophilic a.a. side chains predominate at the protein's surface, in contact with
the water.
4. Quaternary structure. Two or more separate polypeptides, each of which is already folded into
its tertiary structure, may now interact with each other at their surfaces to form a larger protein.
These separate folded polypeptides are called subunits. Picture your 2 closed fists, each
representing a folded polypeptide, pressed together. Some proteins won't function unless they
have this level of structure. Hemoglobin is a good example; it contains 4 separate folded
(tertiary) polypeptides, 2 of one type (alpha chains) and 2 of another type (beta chains). Each
alpha chain contains 141 a.a. and each beta chain 146 a.a. Some proteins, but certainly not all,
have quaternary structure. It is H bonds and ionic interactions that hold the separate proteins
together.
A comment about "protein" versus "polypeptide:" Many people use the two terms
interchangeably. As we will see in Part 2 of the course, when the cellular machinery is actively
manufacturing a protein molecule, it does so by covalently linking a.a together, one by one. If
we could abort that process before it was completed, we would have many a.a. bonded together,
i.e. a polypeptide, but that would not be a functional protein. Similarly, when an ingested protein
molecule is exposed to gastric fluid, the acidity denatures the protein, unfolding it to its primary
structure or very nearly so. The molecule is no longer a functional protein but it is still a
polypeptide, at least until digestive enzymes begin to cleave the peptide bonds in the stomach
and small intestine. That process in which the covalent bonds between monomers of a polymer
are cleaved by adding the components of water (H and OH) is called hydrolysis. Hydrolysis
(verb: hydrolyze) is the reverse of dehydration synthesis. Thus, a polypeptide can be hydrolyzed
to its constituent amino acids; a polysaccharide can be hydrolyzed to its constituent
monosaccharides. And a triglyceride can undergo hydrolysis to yield three fatty acids and one
glycerol molecule. All three of these events are part of digestion of your food.
Strictly from a nutritional point of view, proteins in their native (properly folded) state versus
denatured ones have equal nutritional value. But inside living organisms proteins that are not
properly folded into their native shape do not function properly. Thus, the term protein may be
reserved in some instances to denote intact, properly folded, functional molecules.
Also from a nutritional point of view, proteins may be described as complete or incomplete.
Complete proteins are those that contain all eight of the essential amino acids ( 8 in humans).
These eight amino acids cannot be synthesized from any other dietary components and must,
therefore, be provided in the diet. We saw earlier a similar distinction with the essential fatty
acids (linoleic and linolenic) and essential oils (made from essential fatty acids).
The other dozen or so amino acids can be derived from carbohydrates and fats in the diet; these
are called the nonessential amino acids. Note here that nonessential does not mean unimportant
or not needed.
The same issue defines vitamins, except that vitamins are a structurally diverse group with
members in many different families of organic molecules. In order to avoid health issues
stemming from protein insufficiency in the diet, an individual must consume a sufficient quantity
of protein and a sufficient quality of protein in order to get those essential amino acids. Strict
vegetarians are at risk of protein deficiency because individual plans typically are deficient in
one or more of the eight essential amino acids. By judicious mixing of plant types in the diet,
one can obtain complete protein from plant sources alone. Animal sources (meats, eggs, milks)
provide complete protein.
Functions of proteins: examples
1. Sources of chemical energy, as noted already. When degraded for energy in cells, proteins
produce carbon dioxide, water, and ammonia.
2. Enzymes These proteins catalyze chemical reactions in cells.
3. Carrier proteins embedded in membranes transport ions and organic molecules through
membranes. See facilitated diffusion and active transport.
4. Antibodies are proteins involved in the body’s immune system role in protection against
infectious agents.
5. Oxygen transport: hemoglobin and myoglobin (in muscle cells)