CANCELLED Seminar - Christian Kaiser

photo of Dr. Christian Kaiser
March 16, 2020 - 12:00pm
Location: 
601 Fairchild

Johns Hopkins University

Host: Ruben Gonzalez

Title: Dissecting multi-domain protein folding with optical tweezers

Abstract: Large proteins with multiple domains constitute almost half of all proteins in extant proteomes. Assistance from molecular chaperones and co-translational folding ensure efficient folding of these multi-domain proteins in the cell, but the underlying mechanisms remain poorly understood. Using optical tweezers, we have dissected the folding of elongation factor G (EF-G), a multi-domain protein that requires chaperones for efficient folding. Interactions with the ribosome reduce inter-domain misfolding and, depending on nascent chain length, can either reduce or increase folding rates. Energetic dependencies among domains determine whether folding occurs during translation or after synthesis is complete. Unexpectedly, co-translational folding does not proceed unidirectionally: unfolded polypeptide emerging from the ribosome can denature an already folded domain. The chaperone trigger factor, but not the ribosome, protects against denaturation, thus helping multi-domain proteins overcome inherent challenges during co-translational folding. Our single-molecule experiments define the folding pathway of a complex multi-domain protein and show how the ribosome and molecular chaperones assist nascent chain folding.

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