title: Structure and evolution of the spliceosomal peptidyl-prolyl cis-trans isomerase Cwc27.
abstract: Cwc27 is a spliceosomal cyclophilin-type peptidyl-prolyl cis-trans isomerase (PPIase). Here, the crystal structure of a relatively protease-resistant N-terminal fragment of human Cwc27 containing the PPIase domain was determined at 2.0 Å resolution. The fragment exhibits a C-terminal appendix and resides in a reduced state compared with the previous oxidized structure of a similar fragment. By combining multiple sequence alignments spanning the eukaryotic tree of life and secondary-structure prediction, Cwc27 proteins across the entire eukaryotic kingdom were identified. This analysis revealed the specific loss of a crucial active-site residue in higher eukaryotic Cwc27 proteins, suggesting that the protein evolved from a prolyl isomerase to a pure proline binder. Noting a fungus-specific insertion in the PPIase domain, the 1.3 Å resolution crystal structure of the PPIase domain of Cwc27 from Chaetomium thermophilum was also determined. Although structurally highly similar in the core domain, the C. thermophilum protein displayed a higher thermal stability than its human counterpart, presumably owing to the combined effect of several amino-acid exchanges that reduce the number of long side chains with strained conformations and create new intramolecular interactions, in particular increased hydrogen-bond networks.
authors.affiliation: Laboratory of Structural Biochemistry, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ulrich
authors.affiliation: Laboratory of Structural Biochemistry, Freie Universität Berlin, Takustrasse 6, 14195 Berlin, Germany.
authors.forename: Markus C
authors.initials: MC
authors.lastname: Wahl
mesh_terms: D000595:Amino Acid Sequence; D002597:Chaetomium / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D018360:Crystallography, X-Ray; D021983:Cyclophilins / Q000737:chemistry* / Q000235:genetics; D004795:Enzyme Stability; D006801:Humans; D008969:Molecular Sequence Data; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000235:genetics; D010802:Phylogeny; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: C000600171:Cwc27 protein, human; D021983:Cyclophilins; D019696:Peptidylprolyl Isomerase
keywords: Cwc27; peptidyl-prolyl cis–trans isomerase