(Logo) Proteins - an Overview

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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 function:
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 proteins.

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.

Structural proteins
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.

Protein Structure

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 more emphatically.

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Last updated 22nd Feb '96