Human Pre-mRNA Processing factor 19 (hPRPF19) is an important component in human spliceosome machinery. hPRPF19 contains a WD40 repeats domain at its C-terminus, which is also conserved in yeast. Here we determined the crystal structure of the C-terminal WD40 repeat domain of hPRPF19 by X-ray crystallography. Our structural analysis revealed some significantly different structure features between the human and yeast Prp19 WD40 repeat domain. However, there are also conserved clusters of residues at the bottom surface of the fourth and the fifth WD40 repeats, which provides the important implication for the conserved Prp19 proteins in both human and yeast. (C) 2017 Elsevier Inc. All rights reserved.