Publications J. Klein (2003-2022)

Calmodulin structural dynamics

We unravel how aging and age-related disease cause a decline in muscle function through changes in muscle protein structure and dynamics. We focus on calmodulin, the conductor of the cellular orchestra that accompanies the calcium signal, regulating hundreds of proteins in a calcium-dependent manner. Some protein amino acids, such as methionine, can ‘sense’ cellular physiology by chemically reacting with byproducts of metabolism and aging, and then respond, acting as a redox sensor. I have delineated how a muscle redox sensor works, from (1) the biophysical structural changes that occur within the muscle protein due to oxidation, to (2) the biochemical impacts on protein function, and finally, to (3) changes to cell physiology and aging. *Undergraduate student authors

Steil, A.W.*, Kailing, J.W.*, Armstrong, C.J.*, Walgenbach, D.G.*, and Klein, J.C. (2020) The calmodulin redox sensor controls myogenesis. PLOS ONE 15(9): e0239047.

Walgenbach, D.G.*, Gregory, A.J.*, and Klein, J.C. Unique methionine-aromatic interactions govern the calmodulin redox sensor. Biochemical and biophysical research communications, 505 (2018) 236-241.

McCarthy, M.R.*, Thompson, A.R., Nitu, F., Moen, R.J., Olenek, M.J.*, Thomas, D.D., and Klein, J.C. (shared last authorship) (2015) Impact of methionine oxidation on calmodulin structural dynamics. Biochemical and biophysical research communications 456(2): 567-72.

Redox sensitive amino acids in the actomyosin interface

We examined the reactivity and functional sensitivity of the actomyosin interface to cellular oxidants and antioxidants and discovered that particular methionines in myosin behave as redox sensors because of their susceptibility to reversible oxidative modification. We used high-resolution spectroscopy to measure changes in protein structure and dynamics that resulted from oxidative modification. *Undergraduate student authors

Moen, R. J., Cornea, S., Oseid, D. E., Binder, B. P.*, Thomas, D. D., and Klein, J. C. (shared last authorship) (2014) Redox-sensitive residue in the actin-binding interface of myosin. Biochemical and biophysical research communications. 453(3): 345-9. PMID: 25264102

Moen, R. J., Klein, J. C., and Thomas, D. D. (2014) Electron paramagnetic resonance resolves effects of oxidative stress on muscle proteins. Exercise and sport sciences reviews. 42: 30-36.

Klein, J. C., Smith, E.*, Moen, R. J., Titus, M. A., and D. D. Thomas (2011) Structural Impact of Myosin II Methionine Oxidation. Biochemistry. 50(47): 10318-27.

Functional importance of protein dynamics

A theme of my work has been highlighting the biological importance of protein dynamics. As a graduate student, I developed myosin II as a system for site-directed spectroscopy for measuring dynamics and then found that restricting myosin dynamics within the actin-binding interface caused severe inhibition of actin-activated myosin activity and changes in the structural interaction between actin and myosin. *Undergraduate student authors

Moen, R. J., Thomas, D. D., and Klein, J.C. (2013) Conformationally Trapping the Actin-binding Cleft of Myosin with a Bifunctional Spin Label. Journal of Biological Chemistry. 288(5): 3016-24.

Klein, J.C., Burr, A.R., Svensson, B., Kennedy, D.J., Titus, M.A., Rayment, I., and D. D. Thomas (2008) Actin-Binding Cleft Closure in Myosin II Probed by Site-Directed Spin Labeling and Pulsed EPR. PNAS. 105(36): 13397-13402.

Scholarship of Teaching and Learning

Yu, A., Wisinski, J., Osmundson, T., Sanderfoot, A., Cooper, S., & Klein, J. (2022). Instructional Innovations in College-Level Molecular Bioscience Labs during the Pandemic-Induced Shift to Online Learning. Education Sciences, 12(4), 230.

Cooper, S., Klein, J., & Galbraith, A. (2016). Development of a Client-Based Undergraduate Molecular Biology Laboratory. Council on Undergraduate Research Quarterly. 36(4).

Biological Mathematics

Klein, J.C., and Thomas Sibley (2003) Taking the Sting out of Wasp Nests: A Dialogue on Modeling in Mathematical Biology. College Mathematics Journal. 34(3): 207-215.