GBB Seminar Christian Kaiser April 23 / 4.15pm / room 5159.0029

Christian Kaiser Utrecht University

Dissecting protein folding on the ribosome - from single molecules to cells

My group is interested in understanding the folding and structural dynamics of proteins, with a focus of multi-domain proteins. We are using single-molecule manipulation with optical tweezers to dissect folding pathways and resolve structural dynamics. To provide biological context, we are complementing these high-resolution measurements with cellular assays. I will present recent and ongoing work in these areas. (1) We developed a reporter assay for co-translational folding has allowed us to map the folding pathway of structurally complex protein domains in the cellular environment. Employing this tool, we show how domain topology shapes folding pathways and map interactions with molecular chaperones during co-translational folding. (2) Kinetic stability protects proteins against transient unfolding, which may otherwise result in aggregation. By dissecting the co- translational folding pathway of a kinetically hyperstable protein, we discovered how the ribosome

stabilizes a co-translational folding intermediate, catalyzing formation of the native structure.