title: The multiple forms of bovine seminal ribonuclease: structure and stability of a C-terminal swapped dimer.
abstract: Bovine seminal ribonuclease (BS-RNase) acquires an interesting anti-tumor activity associated with the swapping on the N-terminal. The first direct experimental evidence on the formation of a C-terminal swapped dimer (C-dimer) obtained from the monomeric derivative of BS-RNase, although under non-native conditions, is here reported. The X-ray model of this dimer reveals a quaternary structure different from that of the C-dimer of RNase A, due to the presence of three mutations in the hinge peptide 111-116. The mutations increase the hinge peptide flexibility and decrease the stability of the C-dimer against dissociation. The biological implications of the structural data are also discussed.
authors.affiliation: Department of Chemical Sciences, University of Naples 'Federico II', via Cintia, 80126 Naples, Italy; Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, 80134 Naples, Italy; National Institute Biostructures and Biosystems, Inter-University Consortium, Viale Medaglie d'Oro 305, I-00136 Rome, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Sica
authors.forename: Andrea
authors.initials: A
authors.lastname: Pica
authors.forename: Antonello
authors.initials: A
authors.lastname: Merlino
authors.forename: Irene
authors.initials: I
authors.lastname: Russo Krauss
authors.forename: Carmine
authors.initials: C
authors.lastname: Ercole
authors.forename: Delia
authors.initials: D
authors.lastname: Picone
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D004722:Endoribonucleases / Q000737:chemistry* / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary
chemical_list: D004722:Endoribonucleases; C032523:ribonuclease SPL
keywords: BS-RNase; Bovine seminal ribonuclease; C-terminal 3D domain swapping; Cytotoxic RNase; D(ART)-BS; D(ART)-STAA-BS; DTT; G16S/N17T/P19A/S20A variant of BS-RNase; G16S/N17T/P19A/S20A variant of mBS; Hinge peptide; IAA; L28Q variant of mBS; L28Q-mBS; M=M; Multiple swapping; M×M; NCD-BS; P19A/L28Q variant of BS-RNAse; P19A/L28Q variant of mBS; PALQ-BS-RNase; PALQ-mBS; R80S variant of STAA-BS-RNase; R80S variant of STAA-mBS; R80S-STAA-BS-RNase; R80S-STAA-mBS; RI; RNase A; SEC; STAA-BS-RNase; STAA-mBS; artificial dimer of BS-RNase obtained by incubation in acetic acid of mBS and lyophilisation; artificial dimer of STAA-BS-RNase obtained by incubation in acetic acid of STAA-mBS and lyophilisation; bovine pancreatic ribonuclease (EC 3.1.2.27.5); bovine seminal ribonuclease; covalent swapped isomer of BS-RNase; covalent unswapped isomer of BS-RNase; dithiothreitol; iodoacetamide; mBS; monomeric derivative of BS-RNase with cysteines 31 and 32 either linked to glutathione moieties or alkylated with iodoacetamide; non-covalent swapped dimer of BS-RNase with cysteines 31 and 32 linked to iodoacetamide, obtained by selective reduction of the swapped isoform and iodoalkylation; ribonuclease inhibitor; size-exclusion chromatography