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Pollard and Korn 248 (13): 4682
Pollard and Korn 248 (13): 4691
Maruta and Korn 252 (23): 8329
J. Biol. Chem., Vol. 281, Issue 28, 22, July 14, 2006
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Classics
The Unconventional Myosins and Edward D. Korn
Acanthamoeba Myosin. I. Isolation from Acanthamoeba castellanii of an Enzyme Similar to Muscle Myosin
(Pollard, T. D., and Korn, E. D. (1973) J. Biol. Chem. 248, 4682–4690)
Acanthamoeba Myosin. II. Interaction with Actin and with a New Cofactor Protein Required for Actin Activation of Mg2+ Adenosine Triphosphatase Activity
(Pollard, T. D., and Korn, E. D. (1973) J. Biol. Chem. 248, 4691–4697)
Acanthamoeba Cofactor Protein Is a Heavy Chain Kinase Required for Actin Activation of the Mg2+-ATPase Activity of Acanthamoeba Myosin I
(Maruta, H., and Korn, E. D. (1977) J. Biol. Chem. 252, 8329–8332)
Edward David Korn was born in Philadelphia in 1928. After graduating from high school in 1945, he began undergraduate studies at the University of Pennsylvania as an economics major. He eventually switched his major to chemistry and earned his A.B. in 1949. He applied to graduate school and was accepted into the program at the University of Pennsylvania. Korn received his Ph.D. in 1954, working with Jack Buchanan on purine biosynthesis. He then joined Journal of Biological Chemistry (JBC) Classics author Christian Anfinsen (1) at the National Heart Institute (NHI).
Anfinsen had established a group of young investigators to study the structure and metabolism of plasma lipoproteins, which had recently been implicated in the etiology of coronary artery disease. Korn worked on plasma lipoprotein transport for a while, but eventually his interests shifted to endocytosis. In 1967, he acquired an electron microscope and began to correlate the biochemical events of phagocytosis of latex beads with morphological events at high resolution. A year later he discovered microfilaments in Acanthamoeba castellanii that strongly resembled actin filaments, and by the next year he had purified Acanthamoeba actin. This discovery resulted in a total redirection of his research, and he began to look for myosin, the ATPase that provides energy for the coupled movement of the protein pair, in Acanthamoeba.
Korn's attempts to isolate myosin were unsuccessful when he tried to use purification procedures that had worked for other cells. Then, Evan Eisenberg, a postdoctoral fellow in Wayne Kielley's laboratory, suggested to Korn's postdoctoral fellow Tom Pollard that they make use of the fact that myosins, unlike other ATPases, are active at high ionic strength in the absence of any divalent cation (K-EDTA-ATPase activity). Pollard set about purifying the K-EDTA-ATPase from a pyrophosphate extract of Acanthamoeba utilizing DEAE-chromatography, ammonium sulfate fractionation, and adsorption chromatography on agarose and hydroxyapatite columns. This is the subject of the first JBC Classic reprinted here.
With a molecular weight of 180,000, Korn and Pollard's purified myosin was smaller than other conventional myosins. Surprisingly, they also discovered that the purified myosin required a cofactor in order to be activated by actin. In the second JBC Classic, Korn and Pollard describe the binding of the purified myosin to actin and the partial purification and characterization of the cofactor protein required for the activation of the Mg2+-ATPase by actin. Finally, in the third JBC Classic, Korn and Hiroshi Maruta show that this cofactor is a kinase that phosphorylates the myosin heavy chain. This was the first example of regulation of myosin activity by heavy chain phosphorylation. Korn and his colleagues subsequently purified the kinase (2) and identified the phosphorylation site (3).
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In the first and second JBC Classics, Pollard and Korn reported that the MgATPase activity of the amoeba myosin was not a simple hyperbolic function of actin concentration, as seen in all previously studied myosins. Instead, it showed a triphasic dependence with high activity at very low actin concentrations, lower activity as the actin concentration was increased, and then rising activity at still higher actin concentrations. The Acanthamoeba myosin monomers also aggregated actin filaments into parallel bundles as if they had two actin-binding sites: one, as in all myosins, in the head domain and another, which previously studied myosins apparently did not have, in the tail domain. In 1988 Korn and his colleagues showed that the triphasic actin dependence was a result of this second actin-binding site (4).
Although the requirement for a cofactor for actin-activated MgATPase activity and the triphasic dependence on actin concentration were unusual for a myosin, the most surprising feature of the Acanthamoeba myosin was that it was a globular protein consisting of a single heavy chain of just 140,000 Da and a single light chain. All other known myosins consisted of an asymmetric dimer of two heavy chains of 
200,000 Da joined together through a rod-like, coiled-coil helical tail and two pairs of light chains.
The idea that Korn's enzyme was a myosin initially met with resistance from muscle biochemists. Many believed that this small myosin was a degradation product of a conventional myosin despite Korn's evidence to show otherwise. Eventually, it was ruled out that the Acanthamoeba myosin was a degradation product of a conventional myosin when a conventional Acanthamoeba myosin was identified. Korn named the original myosin myosin I and the new conventional myosin myosin II.
Although discovery of additional unconventional myosins was initially slow, by 1992 fourteen unconventional myosins had been identified and were divided into four groups. Three years later the myosin superfamily consisted of 11 different classes, and class I, alone, contained about 26 entries. By 2001, at least 150 myosin heavy chain sequences had been identified, falling into 18 classes in phylogenetic trees based on sequences of their head domains.
Korn continues to study actin and myosin at the NIH. For an overview of his subsequent research, see Korn's JBC Reflections (5). After his initial postdoctoral fellowship at the NHI, Korn became an Assistant Scientist, then Senior Assistant Scientist, and eventually a Research Chemist in the Laboratory of Cellular Physiology and Metabolism at the National Heart and Lung Institute (NHLI). In 1969, he became Head of the Section on Cellular Biochemistry and Ultrastructure, Laboratory of Biochemistry at NHLI. Currently, he is Chief of the Laboratory of Cell Biology, and Head of the Section on Cellular Biochemistry and Ultrastructure in the Laboratory of Cell Biology at the National Heart, Lung, and Blood Institute (NHLBI), as well as Director of the Cell Biology and Physiology Center at NHLBI. Korn has also served as the Deputy Scientific Director, Acting Scientific Director, and Scientific Director of the NHLBI.
In recognition of his research on actin and myosin, Korn has been honored with many awards including the United States Public Health Service Superior Service Award (1980), the Presidential Meritorious Executive Rank Award (1987), the NIH Director's Award (1995), and the NIH Merit Award (2001). He was elected to the National Academy of Sciences in 1990. Korn has served on the editorial boards of many journals, including the Journal of Lipid Research, the Journal of Molecular Cardiology, the Journal of Supramolecular Structure, the Journal of Biological Chemistry, the Journal of Mechanochemistry and Cell Motility, Protein Profile, and the Proceedings of the National Academy of Sciences. Korn also served as an Associate Editor for the Journal of Biological Chemistry.1
Thomas Dean Pollard, Korn's coauthor on the JBC Classic, also remains active in actin and myosin research. He is currently a Professor of Molecular Biophysics and Biochemistry at Yale University and the Chair of Yale's Department of Molecular, Cellular and Developmental Biology. Pollard previously served as President of the Salk Institute for Biological Studies (1996–2000) and as a Professor at the Johns Hopkins School of Medicine (1976–1996). In 1996 Pollard received the Rosensteil Award from Brandeis University, and in 2004 he was awarded the E. B. Wilson Medal from the American Society for Cell Biology. Among his numerous publications, Pollard is the coauthor of the textbook Cell Biology. He earned his B.A. from Pomona College in 1964 and his M.D. from Harvard Medical School in 1968.
FOOTNOTES
1 All biographical information on Edward D. Korn was taken from Ref. 5. 
REFERENCES
- JBC Classics: Haber, E., and Anfinsen, C. B. (1962) J. Biol. Chem. 237, 1839–1844 (http://www.jbc.org/cgi/content/full/281/14/e11)
- Hammer, J. A., III, Albanesi, J. P., and Korn, E. D. (1983) Purification and characterization of a myosin I heavy chain kinase from Acanthamoeba castellanii. J. Biol. Chem. 258, 10168–10175
[Abstract/Free Full Text] - Brzeska, H., Lynch, T. J., and Korn, E. D. (1989) The localization and sequence of the phosphorylation sites of Acanthamoeba myosins I. An improved method for locating the phosphorylated amino acid. J. Biol. Chem. 264, 19340–19348
[Abstract/Free Full Text] - Brzeska, H., Lynch, T. J., and Korn, E. D. (1988) Localization of the actin-binding sites of Acanthamoeba myosin IB and effect of limited proteolysis on its actin-activated Mg2+-ATPase activity. J. Biol. Chem. 263, 427–435
[Abstract/Free Full Text] - Korn, E. D. (2004) The discovery of unconventional myosins: serendipity or luck? J. Biol. Chem. 279, 8517–8525
[Free Full Text]
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