Touring the Protein Folding Landscape: the View Depends on How and Where You Look

SUSAN MARQUSEE, UC BERKELEY

Understanding the structural and dynamic information encoded in the primary sequence of a protein is one of the most fundamental challenges in modern biology. The amino acid sequence of a protein encodes more than the native three-dimensional structure; it encodes the entire energy landscape – an ensemble of conformations whose energetics and dynamics are finely tuned for folding, binding and activity. Small variations in the sequence and environment modulate this landscape and can have effects that range from undetectable to pathological. Dr. Marqusee will present her laboratory's recent results probing these sequence and environmental effects using a combination of single-molecule and ensemble-based studies.

Dr. Marqusee will address a fundamental question in protein folding of whether proteins fold through one or multiple trajectories. While most experiments indicate a single pathway, simulations suggest that proteins can fold through many parallel pathways. By using a combination of chemical denaturant, mechanical force and site-directed mutations, Dr. Marqusee's lab has resolved this apparent contradiction. They can detect the presence of multiple unfolding pathways in a simple, two-state folding protein; the dominant pathway can be altered by small changes in the sequence or environment. Dr. Marqusee will explore the implications of this result for 1) protein folding in complex environments, such as in the cell, or on the ribosome, and 2) the suggestion that evolution can modulate both the rates of folding and the specific pathway.

December 3rd, 2015 at 12:15 PM in Clark Center Seminar Room S360

Hosted by:

Pehr Harbury, Associate Professor of Biochemistry

Pre-Seminar December 1st, 2015 at 12:15 PM in Clark S361