Proteins and life
Proteins are abundant in all organisms and are indeed fundamental to life.
The diversity of protein structure underlies the very large range of their
Enzymes- biological catalysts
Most of the chemical reactions which occur in biological systems are catalyzed
by enzymes, which are proteins*. Some relatively straightforward
reactions such as hydration of carbon dioxide and the modification of small
organic molecules are enzyme-catalyzed; at the other end of the scale are
complex transformations of large molecules. Enzymes are involved in the reading
of genetic information stored in DNA, the first step in the synthesis of
proteins themselves. In addition, the non-protein components of cells are
synthesized by enzymes. Thus, enzymes are a central component of "cellular
machinery". The rates of the reactions they catalyze are generally increased
by the order of at least a million-fold.
* In fact, some RNA molecules, called 'ribozymes' have been shown
to have catalytic activity, so that in fact not all enzymes are
Various ions, small molecules and other metabolites are stored by complexing
with proteins; for example haemoglobin carries oxygen and iron is stored
by ferritin in the liver.
Proteins are involved in the transportation of particles ranging from electrons
to macromolecules. Iron is transported by transferrin; haemoglobin occurs
in red blood cells, and so delivers oxygen from lungs to other tissues, and
also plays a role in the transport of carbon dioxide to the lungs. Some proteins
form pores in cellular membranes through which ions pass; the transport of
proteins themselves across membranes also depends on other proteins.
Proteins are involved in the transmission of nervous impulses, by acting
as receptors of small molecules which cross junctions separating nerve cells.
Within an organism, biological processes must be coordinated between cells
in tissues and indeed between different organs. This is achieved by the
signalling molecules called hormones; a number of hormones are proteins (for
example insulin). Proteins also act as hormone receptors.
The immune system depends on the production of antibodies: proteins which
bind to specific foreign particles such as bacteria and viruses.
The information required to synthesize proteins is stored in genes (sequences
of DNA). The precise orchestration of cellular activity requires that the
various gene products (proteins) are present in appropriate quantities at
the correct times. Enzymes synthesize proteins by translating sequences of
DNA, and this production can be promoted or repressed by other proteins,
in complex feedback mechanisms.
Some proteins have a structural role, providing mechanical support. The
"skeleton" of a cell consists of a complex network of protein filaments.
On a larger scale, muscle contraction depends on the action of large protein
assemblies. Other organic material such as hair and bone are also based on
protein. Collagen is found in all multicellular animals, occurring in almost
every tissue. It is the most abundant vertebrate protein; approximately a
quarter of mammalian protein is collagen.
Proteins are linear heteropolymers of fixed length; i.e. a single type of
protein always has the same number and composition of monomers, but different
proteins have a range of monomer units, from a few tens to approximately
a thousand. The monomers are amino acids, and there are 20 types, which
themselves have a range of chemical properties. There is therefore a great
diversity of possible protein sequences. The linear chains fold into specific
three-dimensional conformations, which are determined by the sequence of
amino acids; proteins are generally self-folding. The three-dimensional
structures of proteins are therefore also extremely diverse, ranging from
completely fibrous, to globular.
Protein structures can be determined to an atomic level by X-ray diffraction
and neytron-diffraction studies of crystallized proteins, and more recently
by nuclear magnetic resonance (NMR) spectroscopy of proteins in solution.
However there are many proteins whose structures cannot yet be solved.
Protein sequences are encoded in DNA, the holder of genetic information,
which is itself a linear molecule composed of four types of "base" (monomers
which act as "letters" of the genetic alphabet. In principle, it should
therefore be possible to translate a gene sequence into an amino acid sequence,
and to predict the three-dimensional structure of the resulting chain from
this amino acid sequence. However, there are numerous problems which make
this very difficult, as we shall see later on.
The field of research dealing with the prediction of structure from sequence
is generally known as bioinformatics.
The reason that this field is so important is that the structure of a proteins
is of course intrinsically related to its function. Experimental structure
determination, or structure prediction, aids the elucidation of protein function;
conversely, synthetic protein sequences might be designed so that the protein
performs a desired function.
The study of protein structure is therefore not only of fundamental scientific
interest in terms of understanding biochemical processes, but also produces
very valuable practical benefits.
Benefits- past, present and future
The understanding of enzyme function allows the design of drugs which inhibit
specific enzyme targets for therapeutic purposes. Proteins can themselves
be designed to an extent; for example, a current area of research focusses
on the engineering of insulin so that it dissociates into its active form
more readily, and therefore would quicken the response if injected into a
diabetic patient. Gene technology has also allowed the mass production of
human insulin in microorganisms, for use in the treatment of diabetes.
Just as therapeutic proteins and drugs can be produced for medical and vetinary
purposes, so can knowledge of protein structure and function be used to treat
diseases of plants, and to modify growth and development of crops; for example
the production of "stay-ripe" fruits.
Protein engineering has potential for the synthesis of enzymes to carry out
various industrial processes on a mass scale. For instance, there is currently
a good deal of research into the use of lipases for the industrial breakdown
of fats. A domestic example of the application of protein science is the
introduction of biological detergents, containing enzymes.
The manipulation of genes and their protein products
A typical cell synthesizes approximately 15000 different proteins;
of these, about 2000 are abundant, with over 50000 copies present. There
are only minute amounts of the remainer. The traditional problems of protein
research, i.e. purification of minute homogenous quantities from tissues,
have been conquered with the advent of recombinant DNA technology.
The discovery of the structure of DNA, methods to sequence DNA and the discovery
of restriction endonucleases have made it possible to extract a known gene
from an organism and amplify it by inserting (cloning) it into a fast-growing
microorganism (i.e. in vivo). Recently the polymerase chain
reaction has allowed the amplification of any gene (in vitro).
Developments in the 1970s made it possible to "trick" the host organism to
translate the foreign gene and produce a functional protein product, for
example the production of insulin or growth hormone in bacteria.
The Beauty of Protein Structure
Last but not least, what we also hope you will agree while following this
course is that protein structures, (or at least the models used to represent
them) are often remarkable to behold, and indeed aesthetically pleasing.
The advances in computer graphics enable this to be demonstrated all the
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