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Protein Moonlighting in Biology and Medicine (Hardcover) (Brian Henderson & Mario A. Fares & Andrew C.
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Of the two major products of the gene (proteins and microRNAs) it is the protein that is the functional unit of biology. A combinatorial association of 20 amino acids in linear chains of up to 30,000 residues generates, or can generate in theory, many more proteins than there are stars in our universe. The protein molecule can be chemically active, in the form of an enzyme, whose catalytic effect can speed up chemical reactions by a thousand- to a million-fold. It can be a structural component acting as a tissue support or allowing the transmission of force. It can function as a binding protein, acting to transport other molecules or atoms or act as a receptor binding its ligand to transmit information into the cell.
Proteins are vitally important for life, and this is clearly indicated by the number of genetic diseases whose symptoms are due to altered protein sequences. The classic example of this is sickle cell disease, due to a single amino acid substitution in haemoglobin, resulting in a protein that aggregates when deoxygenated causing massive structural changes in circulating erythrocytes. The function of proteins can be explained by the evolution in the protein of a specific interaction between amino acids to generate what is termed an active site.
Not stated in the central dogma, but generally taken for granted, was that each protein product of the gene had one single biological function. This one-protein-one-function hypothesis was falsified by the first example of a protein exhibiting two functions. In addition, the transparency of a protein is not really a functional property but is a physical property of these molecules. So it was not until the 1990s that additional examples of proteins exhibiting more than one function were identified and another term to describe this phenomenon was introduced. Connie Jeffery, from the University of Chicago, introduced the term Protein Moonlighting in 1999 for the phenomenon of proteins having more than one unique biological function. Since the introduction of the term, protein moonlighting, a slow trickle of serendipitous discoveries of moonlighting proteins has been made such that at the time of writing over one hundred examples of such proteins have been made. While this is a small number of examples, it is possibly only the tip of the iceberg that is the proportion of moonlighting proteins in biology.
Protein moonlighting has only come to prominence in the last 15 years. Although only a small number of protein families have been found to moonlight, the consequences of such additional activities are already known to be of significance in both biological and pathological/medical terms. Moonlighting proteins are known to be involved in human diseases such as cancer and there is rapidly emerging evidence for a major role for protein moonlighting in the infectious diseases. Protein moonlighting has potential consequences for various branches of biology.