Dr. David Draper
Joint-Appointed Faculty
Professor, Chemistry

Johns Hopkins University
Department of Chemistry
3400 North Charles Street
154 Remsen Hall
Baltimore, MD 21218
410-516-7448 Office
410-516-8420 Fax
draper@jhu.edu
Lab Home Page

Studies of RNA Structure and RNA-Protein Interactions

"RNA folding" has become a vigorous area of research as many unexpected and important functional roles have been discovered for RNA molecules. Research in my lab is concerned with two related questions about RNA: What are the energetics of folding compact RNA tertiary structures? How do proteins recognize specific RNA sites and carry out specific tasks? A variety of physical, biochemical, and genetic techniques are being used to explore several RNA systems.

For a number of years, we have used ribosomal protein - RNA complexes as systems to explore different aspects of protein - RNA recognition and RNA folding. Most of our current efforts in this area concern two highly conserved regions of the ribosome that bind elongation factor G (EF-G), which catalyzes GTP hydrolysis and translocation of the ribosome along the messenger RNA. Each region consists of a ribosomal RNA fragment and several ribosomal proteins; assembly of these complexes and their interactions with EF-G are being studied by physical methods. Mutations whose properties are known from the in vitro studies are being introduced into ribosomes in vivo, to probe the functional significance of the complexes that are being prepared. Initial work in this area resulted in the first crystal structure of a ribosomal protein - RNA complex (Conn et al., 1999), which, in conjunction with solution thermodynamic studies, has yielded considerable insight into protein - RNA recognition mechanisms and unexpected features of RNA tertiary folding. Our crystallographic efforts are being carried out in collaboration with Prof. Ed Lattman's laboratory in the Biophysics Department.

In the last few years we have been particularly concerned with electrostatic aspects of RNA. Folding of an RNA tertiary structure is opposed by the unfavorable free energy needed to bring negatively charged phosphates into proximity, and it has long been known that Mg(2+) is much more effective than monovalent ions at reducing the electrostatic free energy of RNA tertiary folds. We have recently developed a theoretical framework for describing cation interactions with RNA. The model successfully accounts for the special properties of Mg(2+), and we are making direct experimental measurements of Mg(2+) - RNA interactions to further test our predictions. In other work, we are examining the electrostatic component of protein - RNA binding, and again are making measurements in simple peptide - RNA complexes to test our theoretical predictions quantitatively.

Selected Publications: