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Proteins are homogeneous polypeptides and amino acids are their building blocks

المؤلف:  Zlatanova, J., & van Holde, K. E.

المصدر:  Molecular Biology: Structure and Dynamics of Genomes and Proteomes (2023)

الجزء والصفحة:  2nd Edition , p42

2026-10-13

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Svedberg’s result, together with earlier hypotheses, provided for the first time a working model for protein structure: proteins were now recognized to be very large macromolecular polymers of amino acids (see below), and many were remarkably uniform in size. By about 1935, this view was shared by most biochemists. But, as so often in science, this led to a new and deeper puzzle: how could the cell so accurately make such a structure over and over again? It could not just be hooking amino acids together randomly. The observation that all of the molecules of a particular protein were of the same size suggested that all had the same sequence of amino acids. But how could such uniformity in sequence be accomplished? Even a small protein can have a polypeptide chain of 100 amino acids. With 20 different amino acids to choose from at each point, there are 20¹⁰⁰ possible sequences: an enormous number—far greater than the count of all the atoms in the universe. A cell could never make the same sequence twice purely by chance!

There was one seemingly easy solution to the dilemma—which proved to be a dead end. Suppose proteins were put together from repetitive units of small peptides, using specific enzymes to add each kind. By the 1930s, the remarkable versatility of enzymes was known to all biochemists, so such models had appeal. There were even experimental results that seemed to support this idea— for example, fibroin, the protein that mostly constitutes silk fibers, released a substantial fraction of repetitive peptides on hydrolysis. However, no such patterns were observed with most proteins, so this did not seem to be a viable general hypothesis. (Curiously, it turns out that many polysaccharides, polymers of simple sugars, are made in just this way.) The ultimate solution to the problem demanded determination of the unique amino acid sequence (if such existed) of at least one protein. That required a whole set of new separation techniques and a new approach to sequencing polypeptide chains.