Crystal structure of a complex between human spliceosomal cyclophilin H and a U4/U6 snRNP-60K peptide.
The spliceosomal cyclophilin H is a specific component of the human U4/U6 small nuclear ribonucleoprotein particle, interacting with homologous sequences in the proteins U4/U6-60K and hPrp18 during pre-mRNA splicing. We determined the crystal structure of the complex comprising cyclophilin H and the cognate domain of U4/U6-60K. The 31 amino acid fragment of U4/U6-60K is bound to a region remote from the cyclophilin active site. Residues Ile118-Phe121 of U4/U6-60K expand the central beta-sheet of cyclophilin H and the side-chain of Phe121 inserts into a hydrophobic cavity. Concomitantly, in the crystal the cyclophilin H active site is occupied by the N terminus of a neighboring cyclophilin H molecule in a substrate-like manner, indicating the capacity of joint binding to a substrate and to U4/U6-60K. Free and complexed cyclophilin H have virtually identical conformations suggesting that the U4/U6-60K binding site is pre-shaped and the peptidyl-prolyl-cis/trans isomerase activity is unaffected by complex formation. The complex defines a novel protein-protein interaction mode for a cyclophilin, allowing cyclophilin H to mediate interactions between different proteins inside the spliceosome or to initiate from its binding platforms isomerization or chaperoning activities.
Reidt
Ulrich
U
Abteilung für Zelluläre Biochemie, Max-Planck-Institut für Biophysikalische Chemie, 37077 Göttingen, Germany.
Wahl
Markus C
MC
Fasshauer
Dirk
D
Horowitz
David S
DS
Lührmann
Reinhard
R
Ficner
Ralf
R
D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D021983:Cyclophilins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019696:Peptidylprolyl Isomerase / Q000737:chemistry*; D010802:Phylogeny; D011485:Protein Binding; D011487:Protein Conformation; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000737:chemistry*; D017381:Spliceosomes / Q000737:chemistry*
D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D021983:Cyclophilins; C476730:cyclophilin H, human; D019696:Peptidylprolyl Isomerase