Biasing conformational mobility of unstructured proteins by macromolecular crowding
EMSL Project ID
29691
Abstract
Macromolecular crowding is an entropic, excluded volume effect that occurs in the presence of inert macromolecules and has both thermodynamic and hydrodynamic consequences. The primary thermodynamic consequences are to bias conformational isomerizations to more compact states and to bias association reactions to the fully bound state. The effect of macromolecular crowding on conformational isomerizations is especially acute for the class of proteins that do not form compact globular structures. Proteins that do not from compact globular structures are referred to as intrinsically unstructured or intrinsically disordered. In dilute solution, intrinsically unstructured proteins form a broad heterogeneous ensemble of structures that undergo conformation fluctuations on multiple timescales and their prevalence in nature is forcing the structural biology community to reassess the protein structure/function paradigm. In this proposal, we are requesting access to the EMSL spectrapolarimeter to determine whether the biasing of conformational isomerizations due to macromolecular crowding is accompanied by an increase in secondary structure for the intrinsically unstructured transactivation domain of the human tumor suppressor, p53. In short, CD spectroscopy will be used to determine whether intensity changes observed in 1H-15N HSQC NMR data are accompanied by an increase in secondary structure.
Project Details
Project type
Limited Scope
Start Date
2008-03-24
End Date
2008-05-24
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members