title: Identification and characterization of Moca-cyp. A Drosophila melanogaster nuclear cyclophilin.
abstract: Cyclophilins are enzymes catalyzing the cis-trans isomerization of peptidyl-prolyl bonds and belong to the enzyme class of peptidyl-prolyl cis-trans isomerases (PPIases), which includes two more families (FK506 binding proteins and parvulins). We report the characterization of a novel cyclophilin (Moca-cyp) isolated from Drosophila melanogaster. The single-copy Moca-cyp gene, which is localized on chromosome 3R, was cloned and sequenced. The sequence alignment of the gene against Moca-cyp cDNA allowed us to define its intron/exon structure and to identify a variant cDNA corresponding to an alternatively spliced mRNA. By embryo in situ RNA hybridization and immunostaining, we show that the expression of Moca-cyp is regulated during embryogenesis of Drosophila. The 120-kDa nuclear Moca-cyp protein belongs to a subfamily of large cyclophilins sharing structural and enzymatic features: their highly conserved N-terminal PPIase domain is extended by a positively charged and divergent C-terminal tail. Compared with cyclophilin 18, the enzymatic activity carried by the PPIase domain of Moca-cyp is low, exhibits characteristic substrate specificity, and shows a reduced sensitivity to the drug cyclosporin A (CsA). The reduced affinity for CsA is one of the typical features linking members of this subfamily and is probably the consequence of two amino acid substitutions within their active site. Another structural feature shared by members of this subfamily is a conserved polypeptidic segment ("moca" domain) that we report for the first time. The moca domain is located within the C-terminal tail and is the exclusive hallmark of a group of large cyclophilins found in multicellular organisms of the animal kingdom.
authors.affiliation: Laboratoire de Génétique Oncologique, UMR1599, Institut Gustave Roussy-PR1, 39 rue Camille Desmoulins, Villejuif 94805 cedex, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Cavarec
authors.forename: Thilo
authors.initials: T
authors.lastname: Kamphausen
authors.forename: Bérangère
authors.initials: B
authors.lastname: Dubourg
authors.forename: Isabelle
authors.initials: I
authors.lastname: Callebaut
authors.forename: Françoise
authors.initials: F
authors.lastname: Lemeunier
authors.forename: Didier
authors.initials: D
authors.lastname: Métivier
authors.forename: Jean
authors.initials: J
authors.lastname: Feunteun
authors.forename: Gunter
authors.initials: G
authors.lastname: Fischer
authors.forename: Nazanine
authors.initials: N
authors.lastname: Modjtahedi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D021983:Cyclophilins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D018076:DNA, Complementary; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D004331:Drosophila melanogaster; D017403:In Situ Hybridization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D018076:DNA, Complementary; D029721:Drosophila Proteins; C468774:Moca-cyp protein, Drosophila; D009687:Nuclear Proteins; D021983:Cyclophilins