BIOT 23 |
| Detailed structural information from hydrogen exchange and related experiments indicate the following three physical principles underlying protein folding pathways. (1) Proteins are made up of small cooperative unfolding/folding submolecular units known as foldons. (2) Proteins construct these foldon pieces to progressively build their final native states using the sequential stabilization principle where pre-formed foldons guide and template the subsequent foldons. (3) Ubiquitous optional misfolding errors can corrupt different naturally occurring on-pathway intermediates and cause intermediates to accumulate by inserting error-repair barriers at different points along the pathway. The first two principles dictate that the folding pathway of a protein gets predetermined by its component foldon substructure, and the order of steps is set by the way the foldon units are organized in the native structure. The third principle dictates whether the pathway appears to be kinetically 2-state or multi-state or heterogeneous. The integration of these three well-documented principles into a coherent mechanism provides a unifying explanation for how proteins fold and why they fold in that way. |
|
Biophysical and Biomolecular Symposium: Protein Folding & Characterization
8:00 AM-11:10 AM, Sunday, August 19, 2007 BCEC -- 106, Oral
Division of Biochemical Technology |