SOLUTION STRUCTURE OF A GAAA TETRALOOP RECEPTOR RNA

The GAAA tetraloop receptor is an Il-nucleotide RNA sequence that part icipates in the tertiary folding of a variety of large catalytic RNAs by providing a specific binding site for GAAA tetraloops. Here we repo rt the solution structure of the isolated tetraloop receptor as solved by multidimensional, heteronuclear magnetic resonance spectroscopy. T he internal loop of the tetraloop receptor has three adenosines stacke d in a cross-strand or zipper-like fashion. This arrangement produces a high degree of base stacking within the asymmetric internal loop wit hout extrahelical bases or kinking the helix. Additional interactions within the internal loop include a U.U mismatch pair and a G.U wobble pair. A comparison with the crystal structure of the receptor RNA boun d to its tetraloop shows that a conformational change has to occur upo n tetraloop binding, which is in good agreement with previous biochemi cal data. A model for an alternative binding site within the receptor is proposed based on the NMR structure, phylogenetic data and previous crystallographic structures of tetraloop interactions.