Viral Proteins by X-ray Diffraction: Ralph Wyckoff and Robert Corey
Year: 2002
Type: article
Abstract: X-ray Diffraction Patterns of Crystalline Tobacco Mosaic Proteins (Wyckoff, R. W. G., and Corey, R. B. (1936) J. Biol. Chem. 116, 51–55) The Journal of Biological Chemistry (JBC) Classic paper reprinted here represents one of the first published in the Journal on the use of x-ray diffraction to study protein structure. The paper is interesting albeit predicated on the misconception that tobacco mosaic virus is a pure protein and nothing else. Such a misconception no doubt resulted from and contributed to the prevailing view of the time that genes were proteins. Ralph W. G. Wyckoff (1897–1994) received his B.S. degree in chemistry from Hobart College in his hometown of Geneva, New York. He entered Cornell University in Ithaca to study astronomy but became interested in x-ray crystallography thanks to S. Nishikawa who was on leave in the physics department. With Nishikawa as his thesis advisor, Wyckoff determined the structures NaNO3 and CsICl2. He received the Ph.D. degree in 1919 at the age of 21. After completing his thesis work, Wyckoff worked at the Geophysical Laboratory in Washington D. C. continuing to apply x-ray analysis to the study of minerals. His approach, like that of Nishikawa, was to collect x-ray diffraction data from multiwavelength Laue patterns and powder patterns. This analysis relied on space group theory and not on diffraction intensities in marked contrast to the British crystallographers who, using monochromatic radiation, regarded quantitative intensity measurements as essential. These issues were controversial until the study of more complicated structures like proteins required knowledge of both space groups and quantitative intensities. Wyckoff published several books including the The Structure of Crystals in 1924, a compilation of structural data available at the time. This book was last updated in 1971 (1Drenth J. Acta Crystallogr. 1995; 51 (Obituary of Ralph W. G. Wyckoff (1897–1994)): 649-650Crossref Google Scholar). Robert B. Corey. Photo courtesy of the Archives, California Institute of Technology.View Large Image Figure ViewerDownload (PPT) Wyckoff moved to the Rockefeller Institute for Medical Research in 1927 with the intention of applying x-ray analysis to organic molecules. He completed the structure of urea and had started on the amino acid glycine with the intention of studying proteins. Robert B. Corey joined Wyckoff in this work, and the two worked together for 10 years, publishing 18 papers. Unfortunately, the Rockefeller Institute lost interest in x-ray crystallography. In 1937 Wyckoff's laboratory was closed, and he was dismissed. During the next 15 years he held several positions including those in industrial laboratories, the University of Michigan, and the National Institutes of Health. He became an electron microscopist and continued his study of proteins and viruses. He was involved also in the founding of the International Union of Crystallographers serving as Vice President and President from 1951 to 1957. He completed his scientific career at the University of Arizona as Professor of Physics and Microbiology, from which he retired at the age of 80. Robert B. Corey (1897–1971) received his B.S. degree in Chemistry from the University of Pittsburgh in 1919. About that time, he contracted polio, which left him with a paralyzed left arm, a limp, and a “frail constitution” (2Marsh R.E. Biographical Memoir of Robert Brainard Corey.72. National Academy of Sciences, Washington D. C.1997: 51Google Scholar). He attended Cornell University and received the Ph.D. degree in inorganic chemistry in 1924. After completing his thesis research, Corey stayed at Cornell as Instructor of Analytical Chemistry and became fascinated with one of the first GE x-ray spectrometers, which Ralph Wyckoff had used a few years earlier. Corey decided to join Wyckoff at the Rockefeller Institute, and the two began a systematic analysis of C–C and C–N bonds as prelude to the study of proteins., When Wyckoff was dismissed by the Rockefeller Institute, Corey was given a one-year fellowship “to be used in any institution where I could profitably continue my crystal structure studies” (2Marsh R.E. Biographical Memoir of Robert Brainard Corey.72. National Academy of Sciences, Washington D. C.1997: 51Google Scholar). Corey wrote to Linus Pauling at the California Institute of Technology who was becoming interested in the structure of biological macromolecules. Pauling replied to Corey's letter, “I would be very glad indeed to have you spend the year in Pasadena” offering an appointment as a research fellow without stipend. Pauling added “so far as I can tell, there would be no possibility for you to be added to the staff at the end of the year.” Pauling may have been as interested in Corey's equipment as he was in Corey and wrote“ Apparatus which we do not have and which you might well need for your work would include a Weissenberg camera, a simple spectrometer for rapid measurement of intensities, a special apparatus for taking powder photographs etc.” (2Marsh R.E. Biographical Memoir of Robert Brainard Corey.72. National Academy of Sciences, Washington D. C.1997: 51Google Scholar). (Apparently the Weissenberg camera was used at Caltech for over 40 years after Corey's arrival (2Marsh R.E. Biographical Memoir of Robert Brainard Corey.72. National Academy of Sciences, Washington D. C.1997: 51Google Scholar).) In spite of Pauling's caveat about future employment, Corey had, by 1949, risen through the ranks to become Professor of Structural Chemistry at Caltech. He and Pauling collaborated until 1964, when Pauling left Caltech. Corey became professor emeritus in 1968 and died in 1971. Corey's work at Caltech began with determining the structures of three small molecules, glycine, alanine, and diketopiperazine (the cyclic anhydride of the dipeptide glycylglycine). These three molecules were among the first organic molecules to have their structures determined. Glycine and alanine were the first amino acids and diketopiperazine the first peptide. The measurements, and especially the calculations of diffraction intensities, for these studies, about 300 for alanine, were a prodigious undertaking considering that the computing aids were a slide rule and an adding machine. From the analysis of diketopiperazine came the critically important data demonstrating that the peptide bond is planar. During World War II, Pauling was asked to lead a project to evaluate the stability and explosive characteristics of various forms of gunpowder. Pauling put Corey in charge of administration of the projects and dealing with the bureaucracy of the War Department. Only after the war was Corey able to return to research. By the late 1940s, Pauling had developed the notion that polypeptide chains in proteins, particularly fibrous proteins like those in hair, muscle, and tendons, which gave good diffraction patterns suggesting extended chains, might form helical structures. With the experimental work as background, Corey and Pauling constructed helical models and demonstrated that one, theα -helix, was compatible with the diffraction data. In addition, they were able to demonstrate the existence of both parallel and anti-parallelβ -sheet structures. This work was published in a set of papers in the Proceedings of the National Academy of Sciences (3Corey R.B. Branson H.R. Pauling L. The structure of proteins: two hydrogen-bonded helical configurations of the polypeptide chain.Proc. Natl. Acad. Sci. U. S. A. 1951; 37: 205-211Crossref PubMed Scopus (1941) Google Scholar, 4Corey R.B. Pauling L. The pleated sheet, a new layer configuration of polypeptide chains.Proc. Natl. Acad. Sci. U. S. A. 1951; 37: 251-256Crossref PubMed Scopus (409) Google Scholar, 5Corey R.B. Pauling L. Configurations of polypeptide chains favored orientation around single bonds: two new pleated sheets.Proc. Natl. Acad. Sci. U. S. A. 1951; 37: 729-740Crossref PubMed Google Scholar) and was a landmark of the beginning of molecular biology! Corey's work relied on model building and required that atomic models be constructed in the Caltech shop to precise dimensions of bond angles and distances and atomic radii. Eventually, these evolved into accurate space-filling models that were relied upon by a generation of chemists and biologists. These CPK models were named for Corey, Pauling, and Walter Koltun, who oversaw their construction. In the final years of his career, Corey worked on the structure of lysozyme and had collected a great deal of data from various crystal forms with heavy atom replacements when the structure was published by D. C. Philips (6Philips D.C. The hen egg-white lysozyme molecule.Proc. Natl. Acad. Sci. U. S. A. 1967; 57: 484-495Crossref Google Scholar). This was an enormous disappointment to Corey and signaled the end of his research career. He retired in poor health in 1968 and died in 1971 (2Marsh R.E. Biographical Memoir of Robert Brainard Corey.72. National Academy of Sciences, Washington D. C.1997: 51Google Scholar).
Source: Journal of Biological Chemistry
Language: English
Subfield: Materials Chemistry
Field: Materials Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
OpenAlex ID: W1568395748