The splicing factor Prp18 is required for the second step of pre-mRNA splicing. The structure of a large fragment of the Saccharomyces cerevisiae Prp18 is known. This fragment is fully active in yeast splicing in vitro and includes the sequences of Prp18 that have been evolutionarily conserved. The core structure consists of five alpha-helices that adopt a novel fold. The most highly conserved region of Prp18, a nearly invariant stretch of 19 aa, forms part of a loop between two alpha-helices and may interact with the U5 small nuclear ribonucleoprotein particles.