Folding and catalysis by the hairpin ribozyme

Abstract

The hairpin ribozyme undergoes a site-specific transesterification cleavage of the phosphodiester backbone. The natural form of the ribozyme is a four-way helical junction, where two arms contain unpaired loops. This folds by pairwise coaxial stacking of helical arms, and a rotation into an antiparallel conformation in which there is close association between the loops. This probably generates the local conformation required to facilitate the trajectory into an in-line SN2 transition state. Folding is induced by the cooperative binding of at least two divalent metal ions, which are probably distributed between the junction and the loop-loop interface. The junction forms the structural scaffold on which the geometry of the ribozyme is built, and structural perturbation of the junction leads to impaired catalytic activity.