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K-State Today

September 18, 2018

Christian Kaiser featured speaker for Biochemistry and Molecular Biophysics Seminar Sept. 19

Submitted by Biochemistry and Molecular Biophysics

Christian Kaiser, assistant professor of biophysics at Johns Hopkins University, will be the featured speaker for Biochemistry and Molecular Biophysics Seminar at 4 p.m. on Sept. 19 in 120 Ackert Hall. He will present "The ribosome cooperates with a chaperone to guide multi-domain protein folding."

Kaiser earned his doctorate in biochemistry with Professor F. Ulrich Hartl at the Max Planck Institute of Biochemistry, Martinsried, and Ludwig Maximilian University, Munich, Germany. He proceeded as a postdoctoral fellow, first at University of Texas Medical Branch at Galveston and then at the University of California, Berkeley before joining the faculty at Johns Hopkins University. He currently holds joint appointments in the departments of Biology and Biophysics, as well as in the Johns Hopkins University School of Medicine Department of Biophysics and Biophysical Chemistry. The Kaiser lab is currently interested in learning how cells make and maintain functional proteins. They want to understand — at a mechanistic level — the molecular machines that synthesize, transport, and fold proteins. Knowing the molecular mechanisms will help to understand how these processes are tuned and synchronized. This knowledge may help in design and production of novel proteins, and understanding the mechanisms underlying protein misfolding, which is observed in a number of diseases.

Presentation abstract: Multidomain proteins — constituting a large group in all proteomes — often require help from molecular chaperones to fold productively, even before the ribosome has finished their synthesis. The mechanisms underlying chaperone function remain poorly understood. We have used optical tweezers to study the folding of elongation factor G (EF-G), a model multidomain protein, as it emerges from the ribosome. We find that the N-terminal G-domain in nascent EF-G polypeptides folds robustly. The following domain II, in contrast, fails to fold efficiently. Strikingly, interactions with the unfolded domain II convert the natively folded G domain to a non-native state. This non-native state readily unfolds, and the two unfolded domains subsequently form misfolded states, preventing productive folding. Both the conversion of natively folded domains and non-productive interactions among unfolded domains are efficiently prevented by the ribosome-binding chaperone trigger factor. Thus, our single-molecule measurements of multidomain protein folding reveal an unexpected role for the chaperone: It protects already folded domains against denaturation resulting from interactions with parts of the nascent polypeptide that are not folded yet. Previous studies had implicated trigger factor in guiding the folding of individual domains, and interactions among domains had been neglected. Avoiding early folding defects is crucial, since they can propagate and result in misfolding of the entire protein. Our experiments define the folding pathway for a complex multidomain protein and shed light on the molecular mechanism employed by the ribosome and molecular chaperones to ensure productive and efficient folding.

The biochemistry and molecular biophysics department is part of the College of Arts and Sciences. Departmental faculty have research programs supported by more than $7 million in extramural support for studying various aspects of biochemistry in animals, plants, insects and microorganisms. Learn more about biochemistry and molecular biophysics at k-state.edu/bmb