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Unformatted text preview: The discovery of the a-helix and b-sheet, the principal structural features of proteins David Eisenberg* Howard Hughes Medical Institute and University of CaliforniaDepartment of Energy Institute of Genomics and Proteomics, University of California, Los Angeles, CA 90095-1570 PNAS papers by Linus Pauling, Robert Corey, and Herman Branson in the spring of 1951 proposed the a-helix and the b-sheet, now known to form the backbones of tens of thousands of proteins. They deduced these fundamental building blocks from properties of small molecules, known both from crystal structures and from Paulings resonance theory of chemical bonding that predicted planar peptide groups. Earlier attempts by others to build models for protein helices had failed both by including nonplanar peptides and by insisting on helices with an integral number of units per turn. In major respects, the PaulingCoreyBranson models were astoundingly correct, including bond lengths that were not surpassed in accuracy for > 40 years. However, they did not consider the hand of the helix or the possibility of bent sheets. They also proposed structures and functions that have not been found, including the g-helix. A decade before the structures of entire proteins were first revealed by x-ray crystallogra- phy, Linus Pauling and Robert Corey of the California Institute of Technology (Fig. 1) deduced the two main structural features of proteins: the a-helix and b-sheet, now known to form the backbones of tens of thousands of proteins. Their deductions, triumphs in building models of large molecules based on features of smaller molecules, were published in a series of eight arti- cles, communicated to PNAS in Febru- ary and March 1951. Their work had a significance for proteins comparable to that 2 years later of the WatsonCrick paper for DNA, which adopted the PaulingCorey model-building approach. Here I summarize the main points of these historic articles, and then mention some surprising omissions from them. The most revolutionary of these arti- cles is the first, submitted to PNAS on Paulings 50th birthday, February 28th, 1951. It is The Structure of Proteins: Two Hydrogen-Bonded Helical Configurations of the Polypeptide Chain (1), in which Pauling and Corey are joined by a third coauthor, H. R. Branson, an African- American physicist, then on leave from his faculty position at Howard Univer- sity (Fig. 1). In the opening paragraph, the authors state that we have been attacking the problem of the structure of proteins in several ways. One of these ways is the complete and accurate deter- mination of the crystal structure of amino acids, peptides, and other simple substances related to proteins, in order that information about interatomic dis- tances, bond angles, and other configu- rational parameters might be obtained that would permit the reliable prediction of reasonable configurations of the polypeptide chain. In other words, the structural chemist Pauling believed that...
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