Title: Disordered RNA-folding chaperones promote nucleic acid conformational transitions via local charge screening
Time: 11:00 a.m.
Location: Room 202 MRB
Presenter: Erik Holmstrom (Assistant Professor, Department of Molecular Biosciences, The University of Kansas, Lawrence, Kansas)
RNA-folding chaperones are an emergent class of proteins that facilitate structure formation in non-coding RNAs and DNAs. These chaperones are involved in many nucleic acid-dependent processes, including critical steps in the life cycles of many viruses. Interestingly, many of these proteins are intrinsically disordered, raising the fundamental question of how such a chaperone functions without a well-defined three-dimensional structure. One such example is the nucleocapsid protein of the hepatitis C virus, which catalyzes viral genome dimerization. Recently, we have uncovered many of the structural and dynamical aspects of chaperone activity using a variety of single-molecule FRET techniques. This positively-charged, intrinsically disordered protein chaperones conformational transitions by acting as a flexible macromolecular counterion that locally screens repulsive electrostatic interactions within the nucleic acid. The resulting compaction biases the unfolded nucleic acid towards compact conformations that are primed for folding, thereby increasing the folding rate constant. Finally, molecular simulations that treat the nucleic acid and chaperone as a simple polyelectrolytes reproduce the experimental observations and support the proposed molecular mechanism of these disordered viral proteins.