Research Abstract:
The mechanism of protein folding is poorly understood. What is the nature of folding intermediates and what are the determinants that control correct folding rather than misfolding. How do dynamics in the unfolded state control the folding process. What is the nature of intrinsically disordered proteins that form aggregates leading to neurodegerative diseases. These are the questions being addressed in this laboratory.
The long-term goal of the protein folding work is to understand the nature of the intermediate structures on the unfolding, refolding and aggregation pathways. Work in the laboratory uses site-directed mutagenesis and techniques such as 19F and proton NMR, circular dichroism, state-of–the-art fluorescence measurements and other biophysical methods. Of particular interest are methods that allow determination of the time dependence of motions in native and unfolded proteins. A variety of proteins are used to address these questions.
Selected Publications:
Frieden, C. Protein aggregation processes: In search of the mechanism. Protein Science 2007 16:2334-2344.
Li H and Frieden C. Observation of sequential steps in the folding of intestinal fatty acid binding protein using a slow folding mutant and 19F NMR. Proc Natl Acad Sci 2007 104:11993-11998.
Crick SL, Jayaraman M, Frieden C, Wetzel R and Pappu RV. Fluorescence correlation spectroscopy shows that monomeric polyglutamine molecules form collapsed structures in aqueous solutions. Proc. Nat’l Acad Sci 2006 103:16764-16769.
Chattophadhyay K, Elson EL, Frieden C. The kinetics of conformational fluctuations in an unfolded protein measured by fluorescence methods. Proc Natl Acad Sci USA 2005 102:2385-2389.
Frieden C. The kinetics of side chain stabilization during protein folding. Biochemistry 2003 42:12439-12446.
Last Updated: 08/18/2008 |