1MZW

Crystal structure of a U4/U6 snRNP complex between human spliceosomal cyclophilin H and a U4/U6-60K peptide

Summary for 1MZW

• Entry DOI: 10.2210/pdb1mzw/pdb
• Related: 1QOI
• Descriptor: U-snRNP-associated cyclophilin, U4/U6 snrnp 60kDa protein (3 entities in total)
• Functional Keywords: cyclophilin, peptidyl-prolyl-cis/trans isomerase, spliceosome, snrnp, u4/u6-60k protein, wd protein, isomerase
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus speckle: O43447; Nucleus speckle (By similarity): O43172
• Total number of polymer chains: 2
• Total formula weight: 22728.16

Authors

Reidt, U.,Wahl, M.C.,Horowitz, D.S.,Luehrmann, R.,Ficner, R. (deposition date: 2002-10-10, release date: 2003-08-19, Last modification date: 2024-02-14)

Primary citation

Reidt, U.,Wahl, M.C.,Fasshauer, D.,Horowitz, D.S.,Luehrmann, R.,Ficner, R.
Crystal structure of a complex between human spliceosomal cyclophilin H and a U4/U6 snRNP-60K peptide
J.Mol.Biol., 331:45-56, 2003

PubMed Abstract: 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.

PubMed: 12875835
DOI: 10.1016/S0022-2836(03)00684-3

Experimental method

X-RAY DIFFRACTION (2 Å)