In which we consider the nature of proteins, how they are synthesized, how they are assembled,, how they get to where they need to go within the cell and the organism, how they function, how their activities are regulated, and how mutations can influence their behavior.
We have mentioned proteins many times, since there are few biological processes that do not rely on them. Proteins act as structural elements, signals, regulators, and catalysts in a wide arrange of molecular machines. Up to this point, however, we have not said much about what they are, how they are made, and how they do what they do. The first scientific characterization of what are now known as proteins was published in 1838 by the Dutch chemist, Gerardus Johannes Mulder (1802–1880)227. After an analysis of a number of different substances, he proposed that all proteins represented versions of a common chemical core, with the molecular formula C400H620N100O120P1S1, and that the differences between different proteins were primarily in the numbers of phosphate (P) and sulfur (S) atoms they contained. The name “protein”, from the Greek word πρώτα (“prota”), meaning “primary”, was suggested by the Swede, Jons Jakob Berzelius (1779–1848) based on the presumed importance of these compounds in biological systems228. As you can see, Mulder’s molecular formula was not very informative, it tells us little or nothing about protein structure, but suggested that all proteins are fundamentally similar, which is confusing since they carry out so many different roles. Subsequent studies revealed that proteins could be dissolved in either water or dilute salt solutions but aggregated and became insoluble when the solution was heated; as we will see this aggregation reaction reflects a change in the structure of the protein. Mulder was able to break down proteins through an acid hydrolysis reaction into amino acids, named because they contained amino (-NH2) and carboxylic acid (-COOH) groups. Twenty different amino acids could be identified in hydrolyzed samples of proteins. Since their original characterization as a general class of compounds, we now understand that while they share a common basic polymer structure, proteins are remarkably diverse. They are involved in roles from the mechanical strengthening of skin to the regulation of genes, to the transport of oxygen, to the capture of energy, to the catalysis and regulation of essentially all of the chemical reactions that occur within cells and organisms.
227 From ‘protein’ to the beginnings of clinical proteomics: http://www.ncbi.nlm.nih.gov/pubmed/21136729
228 While historically true, the original claim that proteins get their name from “the ancient Greek sea-god Proteus who, like your typical sea-god, could change shape. The name acknowledges the many different properties and functions of proteins.” seems more poetically satisfying to us.