Dissertation/Thesis Abstract

Biophysical Characterization of Ribosome Nascent Chain Energy Landscapes
by Samelson, Avi Jacob, Ph.D., University of California, Berkeley, 2017, 123; 10600497
Abstract (Summary)

Protein folding is necessary for proper cellular and organismal function. The disruption of accurate protein folding is highly detrimental to numerous cellular processes and can lead to cell death and disease. A major protein homeostasis node in the cell is the ribosome, which interacts with a number of quality control factors that help guarantee protein folding fidelity. For many years, co-translational folding has been investigated mainly within the context of cellular proteostasis and quality control. Unfortunately, how the ribosome and translational machinery modulates the nascent chain itself has, for the most part, remained a mystery. It is essential to understand how translation changes a protein’s energy landscape during translation in order to understand how folding fidelity can be guaranteed in vivo. Here, I introduce new methods for studying the folding thermodynamics and kinetics of stalled nascent chains and pioneer a new assay for studying folding kinetics during translation in real-time. In addition, I characterize the folding landscape of the protein HaloTag and determine that the process of translation itself increases HaloTag’s folding efficiency by modulating its folding trajectory. The methods developed herein, as well as novel observations about the biophysical properties of nascent chains reported here, pave the way for understanding protein folding in vivo.

Indexing (document details)
Advisor: Marqusee, Susan
Commitee: Cate, Jamie H. D., Savage, David F., Wemmer, David E.
School: University of California, Berkeley
Department: Molecular & Cell Biology
School Location: United States -- California
Source: DAI-B 81/5(E), Dissertation Abstracts International
Subjects: Biophysics, Biochemistry, Biology
Keywords: Co-translational folding, HaloTag, Protein folding, Pulse proteolysis, Ribosome nascent chain
Publication Number: 10600497
ISBN: 9781392791844
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