Crystal structure of the human U4/U6 small nuclear ribonucleoprotein particle-specific SnuCyp-20, a nuclear cyclophilin

The cyclophilin SnuCyp-20 is a specific component of the human U4/U6 small nuclear ribonucleoprotein particle involved in the nuclear splicing of pre- mRNA. It stably associates with the U4/U6-60kD and -90kD proteins, the huma n orthologues of the Saccharomyces cerevisiae Prp4 and Prp3 splicing factor s. We have determined the crystal structure of SnuCyp-20 art 2.0-Angstrom r esolution by molecular replacement. Tbe structure of SnuCyp-20 closely rese mbles that of human cyclophilin A (hCypA), In particular, the catalytic cen ters of SnuCyp-20 and hCypA superimpose perfectly, which is reflected by th e observed peptidyl-prolyl-cis/trans-isomerase activity of SnuCyp-20. The s urface properties of both proteins, however, differ significantly. Apart fr om seven additional amino-terminal residues, the insertion of five amino ac ids in the loop alpha 1-beta 3 and of one amino acid in the loop alpha 2-be ta 8 changes the conformations of both loops. The enlarged loop alpha 1-bet a 3 is involved in the formation of a wide cleft with predominantly hydroph obic character, We propose that this enlarged loop is required for the inte raction with the U4/U6-60kD protein.