Carl Frieden, Ph.D. Professor Biochemistry and Molecular Biophysics Computational and Molecular Biophysics Program Biochemistry Program Molecular Cell Biology Program
Office Phone: 314-362-3344 Lab Phone: 314-362-3342 Other Phone: FAX: 314-362-7183 Box: 8231 Lab Address: 215 McDonnell Medical Sciences Building Email: frieden@biochem.wustl.edu Website: http://www.biochem.wustl.edu/cflab/ Keywords: biophysics; fluorescence; intrinsically disordered proteins; kinetics; NMR; protein folding Short Research Description: Protein aggregation processes
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: Zhang R, Hu X, Khant H, Ludtke SJ, Chiu W, Schmid MF, Frieden C, Lee J-M. Inter-protofilament interactions between Alzheimer’s Aβ1-42 peptides in amyloid fibrils revealed by cryo-EM, Proc. Natl Acad Sci (USA) 2009 106: 4653-4658 Frieden C. Protein aggregation processes: In search of the mechanism. Protein Science 2007 16:2334-2344. 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: 08/11/2009