Group I self-splicing introns catalyze their own excision from precurs
or RNAs by way of a two-step transesterification reaction. The catalyt
ic core of these ribozymes is formed by two structural domains. The 2.
8-angstrom crystal structure of one of these, the P4-P6 domain of the
Tetrahymena thermophila intron, is described. In the 160-nucleolide do
main, a sharp bend allows stacked helices of the conserved core to pac
k alongside helices of an adjacent region. Two specific long-range int
eractions clamp the two halves of the domain together. a two-Mg2+-coor
dinated adenosine-rich corkscrew plugs into the minor groove of a heli
x, and a GAAA hairpin loop binds to a conserved 11-nucleotide internal
loop. Metal- and ribose-mediated backbone contacts further stabilize
the close side-by-side helical packing, The structure indicates the ex
tent of RNA packing required for the function of large ribozymes, the
spliceosome, and the ribosome.