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. 2004 Jun 1;380(Pt 2):311–327. doi: 10.1042/BJ20031922

Oligomerization of bovine ribonuclease A: structural and functional features of its multimers.

Massimo Libonati 1, Giovanni Gotte 1
PMCID: PMC1224197  PMID: 15104538

Abstract

Bovine pancreatic RNase A (ribonuclease A) aggregates to form various types of catalytically active oligomers during lyophilization from aqueous acetic acid solutions. Each oligomeric species is present in at least two conformational isomers. The structures of two dimers and one of the two trimers have been solved, while plausible models have been proposed for the structures of a second trimer and two tetrameric conformers. In this review, these structures, as well as the general conditions for RNase A oligomerization, based on the well known 3D (three-dimensional) domain-swapping mechanism, are described and discussed. Attention is also focused on some functional properties of the RNase A oligomers. Their enzymic activities, particularly their ability to degrade double-stranded RNAs and polyadenylate, are summarized and discussed. The same is true for the remarkable antitumour activity of the oligomers, displayed in vitro and in vivo, in contrast with monomeric RNase A, which lacks these activities. The RNase A multimers also show an aspermatogenic action, but lack any detectable embryotoxicity. The fact that both activity against double-stranded RNA and the antitumour action increase with the size of the oligomer suggests that these activities may share a common structural requirement, such as a high number or density of positive charges present on the RNase A oligomers.

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Selected References

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  1. Ardelt W., Mikulski S. M., Shogen K. Amino acid sequence of an anti-tumor protein from Rana pipiens oocytes and early embryos. Homology to pancreatic ribonucleases. J Biol Chem. 1991 Jan 5;266(1):245–251. [PubMed] [Google Scholar]
  2. BEERS R. F., Jr Hydrolysis of polyadenylic acid by pancreatic ribonuclease. J Biol Chem. 1960 Aug;235:2393–2398. [PubMed] [Google Scholar]
  3. Balbirnie M., Grothe R., Eisenberg D. S. An amyloid-forming peptide from the yeast prion Sup35 reveals a dehydrated beta-sheet structure for amyloid. Proc Natl Acad Sci U S A. 2001 Feb 20;98(5):2375–2380. doi: 10.1073/pnas.041617698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bardoń A., Sierakowska H., Shugar D. Human pancreatic-type ribonucleases with activity against double-stranded ribonucleic acids. Biochim Biophys Acta. 1976 Jul 8;438(2):461–473. doi: 10.1016/0005-2744(76)90262-x. [DOI] [PubMed] [Google Scholar]
  5. Bartholeyns J., Baudhuin P. Inhibition of tumor cell proliferation by dimerized ribonuclease. Proc Natl Acad Sci U S A. 1976 Feb;73(2):573–576. doi: 10.1073/pnas.73.2.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bennett M. J., Choe S., Eisenberg D. Domain swapping: entangling alliances between proteins. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3127–3131. doi: 10.1073/pnas.91.8.3127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bennett M. J., Schlunegger M. P., Eisenberg D. 3D domain swapping: a mechanism for oligomer assembly. Protein Sci. 1995 Dec;4(12):2455–2468. doi: 10.1002/pro.5560041202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bracale Aurora, Castaldi Francesco, Nitsch Lucio, D'Alessio Giuseppe. A role for the intersubunit disulfides of seminal RNase in the mechanism of its antitumor action. Eur J Biochem. 2003 May;270(9):1980–1987. doi: 10.1046/j.1432-1033.2003.03567.x. [DOI] [PubMed] [Google Scholar]
  9. Bucciantini Monica, Giannoni Elisa, Chiti Fabrizio, Baroni Fabiana, Formigli Lucia, Zurdo Jesús, Taddei Niccolò, Ramponi Giampietro, Dobson Christopher M., Stefani Massimo. Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases. Nature. 2002 Apr 4;416(6880):507–511. doi: 10.1038/416507a. [DOI] [PubMed] [Google Scholar]
  10. CRESTFIELD A. M., STEIN W. H., MOORE S. On the aggregation of bovine pancreatic ribonuclease. Arch Biochem Biophys. 1962 Sep;Suppl 1:217–222. [PubMed] [Google Scholar]
  11. Capasso S., Di Donato A., Esposito L., Sica F., Sorrentino G., Vitagliano L., Zagari A., Mazzarella L. Deamidation in proteins: the crystal structure of bovine pancreatic ribonuclease with an isoaspartyl residue at position 67. J Mol Biol. 1996 Apr 5;257(3):492–496. doi: 10.1006/jmbi.1996.0179. [DOI] [PubMed] [Google Scholar]
  12. Carsana A., Furia A., Libonati M. Influence of protein net charge on the nucleic acid helix-destabilizing activity of various pancreatic ribonucleases. Mol Cell Biochem. 1983;56(1):89–92. doi: 10.1007/BF00228773. [DOI] [PubMed] [Google Scholar]
  13. Chiti F., Taddei N., Bucciantini M., White P., Ramponi G., Dobson C. M. Mutational analysis of the propensity for amyloid formation by a globular protein. EMBO J. 2000 Apr 3;19(7):1441–1449. doi: 10.1093/emboj/19.7.1441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chiti Fabrizio, Stefani Massimo, Taddei Niccolò, Ramponi Giampietro, Dobson Christopher M. Rationalization of the effects of mutations on peptide and protein aggregation rates. Nature. 2003 Aug 14;424(6950):805–808. doi: 10.1038/nature01891. [DOI] [PubMed] [Google Scholar]
  15. Chiti Fabrizio, Taddei Niccolò, Baroni Fabiana, Capanni Cristina, Stefani Massimo, Ramponi Giampietro, Dobson Christopher M. Kinetic partitioning of protein folding and aggregation. Nat Struct Biol. 2002 Feb;9(2):137–143. doi: 10.1038/nsb752. [DOI] [PubMed] [Google Scholar]
  16. Cohen F. E., Prusiner S. B. Pathologic conformations of prion proteins. Annu Rev Biochem. 1998;67:793–819. doi: 10.1146/annurev.biochem.67.1.793. [DOI] [PubMed] [Google Scholar]
  17. D'Alessio G., Di Donato A., Piccoli R., Russo N. Seminal ribonuclease: preparation of natural and recombinant enzyme, quaternary isoforms, isoenzymes, monomeric forms; assay for selective cytotoxicity of the enzyme. Methods Enzymol. 2001;341:248–263. doi: 10.1016/s0076-6879(01)41156-6. [DOI] [PubMed] [Google Scholar]
  18. D'Alessio G., Doskocil J., Libonati M. Action of dimeric hybrids of native and selectively alkylated ribonuclease A on double-stranded ribonucleic acid. Biochem J. 1974 Jul;141(1):317–320. doi: 10.1042/bj1410317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. D'Alessio G. New and cryptic biological messages from RNases. Trends Cell Biol. 1993 Apr;3(4):106–109. doi: 10.1016/0962-8924(93)90166-x. [DOI] [PubMed] [Google Scholar]
  20. D'Alessio G., Zofra S., Libonati M. Action of dimeric ribonucleases on double-stranded RNA. FEBS Lett. 1972 Aug 15;24(3):355–358. doi: 10.1016/0014-5793(72)80390-9. [DOI] [PubMed] [Google Scholar]
  21. Di Donato A., Cafaro V., D'Alessio G. Ribonuclease A can be transformed into a dimeric ribonuclease with antitumor activity. J Biol Chem. 1994 Jul 1;269(26):17394–17396. [PubMed] [Google Scholar]
  22. Di Donato A., Ciardiello M. A., de Nigris M., Piccoli R., Mazzarella L., D'Alessio G. Selective deamidation of ribonuclease A. Isolation and characterization of the resulting isoaspartyl and aspartyl derivatives. J Biol Chem. 1993 Mar 5;268(7):4745–4751. [PubMed] [Google Scholar]
  23. FELSENFELD G., SANDEEN G., VONHIPPEL P. H. THE DESTABILIZING EFFECT OF RIBONUCLEASE ON THE HELICAL DNA STRUCTURE. Proc Natl Acad Sci U S A. 1963 Oct;50:644–651. doi: 10.1073/pnas.50.4.644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. FRESCO J. R., KLEMPERER E. Polyriboadenylic acid, a molecular analogue of ribonucleic acid and desoxyribonucleic acid. Ann N Y Acad Sci. 1959 Sep 4;81:730–741. doi: 10.1111/j.1749-6632.1959.tb49354.x. [DOI] [PubMed] [Google Scholar]
  25. Fruchter R. G., Crestfield A. M. On the structure of ribonuclease dimer. Isolation and identification of monomers derived from inactive carboxymethyl dimers. J Biol Chem. 1965 Oct;240(10):3875–3882. [PubMed] [Google Scholar]
  26. Fruchter R. G., Crestfield A. M. Preparation and properties of two active forms of ribonuclease dimer. J Biol Chem. 1965 Oct;240(10):3868–3874. [PubMed] [Google Scholar]
  27. Fändrich M., Fletcher M. A., Dobson C. M. Amyloid fibrils from muscle myoglobin. Nature. 2001 Mar 8;410(6825):165–166. doi: 10.1038/35065514. [DOI] [PubMed] [Google Scholar]
  28. Garcia-Ortega Lucia, Masip Manuel, Mancheño José M., Oñaderra Mercedes, Lizarbe M. Antonia, García-Mayoral M. Flor, Bruix Marta, Martínez del Pozo Alvaro, Gavilanes José G. Deletion of the NH2-terminal beta-hairpin of the ribotoxin alpha-sarcin produces a nontoxic but active ribonuclease. J Biol Chem. 2002 Mar 15;277(21):18632–18639. doi: 10.1074/jbc.M200922200. [DOI] [PubMed] [Google Scholar]
  29. Gotte G., Bertoldi M., Libonati M. Structural versatility of bovine ribonuclease A. Distinct conformers of trimeric and tetrameric aggregates of the enzyme. Eur J Biochem. 1999 Oct;265(2):680–687. doi: 10.1046/j.1432-1327.1999.00761.x. [DOI] [PubMed] [Google Scholar]
  30. Gotte G., Testolin L., Costanzo C., Sorrentino S., Armato U., Libonati M. Cross-linked trimers of bovine ribonuclease A: activity on double-stranded RNA and antitumor action. FEBS Lett. 1997 Oct 6;415(3):308–312. doi: 10.1016/s0014-5793(97)01147-2. [DOI] [PubMed] [Google Scholar]
  31. Gotte Giovanni, Libonati Massimo, Laurents Douglas V. Glycosylation and specific deamidation of ribonuclease B affect the formation of three-dimensional domain-swapped oligomers. J Biol Chem. 2003 Sep 8;278(47):46241–46251. doi: 10.1074/jbc.M308470200. [DOI] [PubMed] [Google Scholar]
  32. Gotte Giovanni, Vottariello Francesca, Libonati Massimo. Thermal aggregation of ribonuclease A. A contribution to the understanding of the role of 3D domain swapping in protein aggregation. J Biol Chem. 2003 Jan 17;278(12):10763–10769. doi: 10.1074/jbc.M213146200. [DOI] [PubMed] [Google Scholar]
  33. Ilinskaya Olga N., Dreyer Florian, Mitkevich Vladimir A., Shaw Kevin L., Pace C. Nick, Makarov Alexander A. Changing the net charge from negative to positive makes ribonuclease Sa cytotoxic. Protein Sci. 2002 Oct;11(10):2522–2525. doi: 10.1110/ps.0216702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Irie M., Nitta K., Nonaka T. Biochemistry of frog ribonucleases. Cell Mol Life Sci. 1998 Aug;54(8):775–784. doi: 10.1007/s000180050206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Janowski R., Kozak M., Jankowska E., Grzonka Z., Grubb A., Abrahamson M., Jaskolski M. Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping. Nat Struct Biol. 2001 Apr;8(4):316–320. doi: 10.1038/86188. [DOI] [PubMed] [Google Scholar]
  36. Jensen D. E., von Hippel P. H. DNA "melting" proteins. I. Effects of bovine pancreatic ribonuclease binding on the conformation and stability of DNA. J Biol Chem. 1976 Nov 25;251(22):7198–7214. [PubMed] [Google Scholar]
  37. Juan G., Ardelt B., Li X., Mikulski S. M., Shogen K., Ardelt W., Mittelman A., Darzynkiewicz Z. G1 arrest of U937 cells by onconase is associated with suppression of cyclin D3 expression, induction of p16INK4A, p21WAF1/CIP1 and p27KIP and decreased pRb phosphorylation. Leukemia. 1998 Aug;12(8):1241–1248. doi: 10.1038/sj.leu.2401100. [DOI] [PubMed] [Google Scholar]
  38. Karpel R. L., Merkler D. J., Flowers B. K., Delahunty M. D. Involvement of basic amino acids in the activity of a nucleic acid helix-destabilizing protein. Biochim Biophys Acta. 1981 Jun 26;654(1):42–51. doi: 10.1016/0005-2787(81)90134-9. [DOI] [PubMed] [Google Scholar]
  39. Kim J. S., Soucek J., Matousek J., Raines R. T. Mechanism of ribonuclease cytotoxicity. J Biol Chem. 1995 Dec 29;270(52):31097–31102. doi: 10.1074/jbc.270.52.31097. [DOI] [PubMed] [Google Scholar]
  40. Klafki H. W., Pick A. I., Pardowitz I., Cole T., Awni L. A., Barnikol H. U., Mayer F., Kratzin H. D., Hilschmann N. Reduction of disulfide bonds in an amyloidogenic Bence Jones protein leads to formation of "amyloid-like" fibrils in vitro. Biol Chem Hoppe Seyler. 1993 Dec;374(12):1117–1122. doi: 10.1515/bchm3.1993.374.7-12.1117. [DOI] [PubMed] [Google Scholar]
  41. Klink T. A., Woycechowsky K. J., Taylor K. M., Raines R. T. Contribution of disulfide bonds to the conformational stability and catalytic activity of ribonuclease A. Eur J Biochem. 2000 Jan;267(2):566–572. doi: 10.1046/j.1432-1327.2000.01037.x. [DOI] [PubMed] [Google Scholar]
  42. Knaus K. J., Morillas M., Swietnicki W., Malone M., Surewicz W. K., Yee V. C. Crystal structure of the human prion protein reveals a mechanism for oligomerization. Nat Struct Biol. 2001 Sep;8(9):770–774. doi: 10.1038/nsb0901-770. [DOI] [PubMed] [Google Scholar]
  43. LEDOUX L. Action of ribonuclease on certain ascites tumours. Nature. 1955 Feb 5;175(4449):258–259. doi: 10.1038/175258b0. [DOI] [PubMed] [Google Scholar]
  44. LEDOUX L. Action of ribonuclease on two solid tumours in vivo. Nature. 1955 Jul 2;176(4470):36–37. doi: 10.1038/176036a0. [DOI] [PubMed] [Google Scholar]
  45. Leland P. A., Raines R. T. Cancer chemotherapy--ribonucleases to the rescue. Chem Biol. 2001 May;8(5):405–413. doi: 10.1016/s1074-5521(01)00030-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Leroy J. L., Broseta D., Guéron M. Proton exchange and base-pair kinetics of poly(rA).poly(rU) and poly(rI).poly(rC). J Mol Biol. 1985 Jul 5;184(1):165–178. doi: 10.1016/0022-2836(85)90050-6. [DOI] [PubMed] [Google Scholar]
  47. Libonati M., Beintema J. J. Basic charges on ribonuclease molecules and activity towards double-stranded polyribonucleotides. Biochem Soc Trans. 1977;5(2):470–474. doi: 10.1042/bst0050470. [DOI] [PubMed] [Google Scholar]
  48. Libonati M., Bertoldi M., Sorrentino S. The activity on double-stranded RNA of aggregates of ribonuclease A higher than dimers increases as a function of the size of the aggregates. Biochem J. 1996 Aug 15;318(Pt 1):287–290. doi: 10.1042/bj3180287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Libonati M. Degradation of poly A and double-stranded RNA by aggregates of pancreatic ribonuclease. Biochim Biophys Acta. 1971 Jan 28;228(2):440–445. doi: 10.1016/0005-2787(71)90049-9. [DOI] [PubMed] [Google Scholar]
  50. Libonati M., Floridi A. Breakdown of double-stranded RNA by bull semen ribonuclease. Eur J Biochem. 1969 Mar;8(1):81–87. doi: 10.1111/j.1432-1033.1969.tb00498.x. [DOI] [PubMed] [Google Scholar]
  51. Libonati M., Malorni M. C., Parente A., D'Alessio G. Degradation of double-stranded RNA by a monomeric derivative of ribonuclease BS-1. Biochim Biophys Acta. 1975 Aug 6;402(1):83–87. doi: 10.1016/0005-2787(75)90372-x. [DOI] [PubMed] [Google Scholar]
  52. Libonati M. Molecular aggregates of ribonucleases. Some enzymatic properties. Ital J Biochem. 1969 Nov-Dec;18(6):407–417. [PubMed] [Google Scholar]
  53. Libonati M., Palmieri M. How much is secondary structure responsible for resistance of double-stranded RNA to pancreatic ribonuclease A? Biochim Biophys Acta. 1978 Apr 27;518(2):277–289. doi: 10.1016/0005-2787(78)90184-3. [DOI] [PubMed] [Google Scholar]
  54. Libonati M., Sorrentino S. Degradation of double-stranded RNA by mammalian pancreatic-type ribonucleases. Methods Enzymol. 2001;341:234–248. doi: 10.1016/s0076-6879(01)41155-4. [DOI] [PubMed] [Google Scholar]
  55. Libonati M., Sorrentino S., Galli R., La Montagna R., Di Donato A. Degradation of DNA . RNA hybrids by aggregates of pancreatic ribonuclease. Biochim Biophys Acta. 1975 Oct 15;407(3):292–298. doi: 10.1016/0005-2787(75)90096-9. [DOI] [PubMed] [Google Scholar]
  56. Libonati M., Sorrentino S. Revisiting the action of bovine ribonuclease A and pancreatic-type ribonucleases on double-stranded RNA. Mol Cell Biochem. 1992 Nov 18;117(2):139–151. doi: 10.1007/BF00230753. [DOI] [PubMed] [Google Scholar]
  57. Liu Y., Gotte G., Libonati M., Eisenberg D. A domain-swapped RNase A dimer with implications for amyloid formation. Nat Struct Biol. 2001 Mar;8(3):211–214. doi: 10.1038/84941. [DOI] [PubMed] [Google Scholar]
  58. Liu Y., Hart P. J., Schlunegger M. P., Eisenberg D. The crystal structure of a 3D domain-swapped dimer of RNase A at a 2.1-A resolution. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3437–3442. doi: 10.1073/pnas.95.7.3437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Liu Yanshun, Eisenberg David. 3D domain swapping: as domains continue to swap. Protein Sci. 2002 Jun;11(6):1285–1299. doi: 10.1110/ps.0201402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Liu Yanshun, Gotte Giovanni, Libonati Massimo, Eisenberg David. Structures of the two 3D domain-swapped RNase A trimers. Protein Sci. 2002 Feb;11(2):371–380. doi: 10.1110/ps.36602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Makarov Alexander A., Ilinskaya Olga N. Cytotoxic ribonucleases: molecular weapons and their targets. FEBS Lett. 2003 Apr 10;540(1-3):15–20. doi: 10.1016/s0014-5793(03)00225-4. [DOI] [PubMed] [Google Scholar]
  62. Marzotto A., Galzigna L. Molecular aggregation of bovine pancreatic ribonuclease induced by substrate. Arch Biochem Biophys. 1970 Apr;137(2):373–378. doi: 10.1016/0003-9861(70)90451-0. [DOI] [PubMed] [Google Scholar]
  63. Mastronicola M. R., Piccoli R., D'Alessio G. Key extracellular and intracellular steps in the antitumor action of seminal ribonuclease. Eur J Biochem. 1995 May 15;230(1):242–249. doi: 10.1111/j.1432-1033.1995.tb20557.x. [DOI] [PubMed] [Google Scholar]
  64. Matousek J. Ribonucleases and their antitumor activity. Comp Biochem Physiol C Toxicol Pharmacol. 2001 Jul;129(3):175–191. doi: 10.1016/s1532-0456(01)90202-9. [DOI] [PubMed] [Google Scholar]
  65. Matousek J. The effect of bovine seminal ribonuclease (AS RNase) on cells of Crocker tumour in mice. Experientia. 1973;29(7):858–859. doi: 10.1007/BF01946329. [DOI] [PubMed] [Google Scholar]
  66. Matousek Josef, Gotte Giovanni, Pouckova Pavla, Soucek Josef, Slavik Tomas, Vottariello Francesca, Libonati Massimo. Antitumor activity and other biological actions of oligomers of ribonuclease A. J Biol Chem. 2003 Apr 14;278(26):23817–23822. doi: 10.1074/jbc.M302711200. [DOI] [PubMed] [Google Scholar]
  67. Matousek Josef, Poucková Pavla, Soucek Josef, Skvor Jirí. PEG chains increase aspermatogenic and antitumor activity of RNase A and BS-RNase enzymes. J Control Release. 2002 Jul 18;82(1):29–37. doi: 10.1016/s0168-3659(02)00082-2. [DOI] [PubMed] [Google Scholar]
  68. Mazzarella L., Capasso S., Demasi D., Di Lorenzo G., Mattia C. A., Zagari A. Bovine seminal ribonuclease: structure at 1.9 A resolution. Acta Crystallogr D Biol Crystallogr. 1993 Jul 1;49(Pt 4):389–402. doi: 10.1107/S0907444993003403. [DOI] [PubMed] [Google Scholar]
  69. Mosimann S. C., Ardelt W., James M. N. Refined 1.7 A X-ray crystallographic structure of P-30 protein, an amphibian ribonuclease with anti-tumor activity. J Mol Biol. 1994 Mar 4;236(4):1141–1153. doi: 10.1016/0022-2836(94)90017-5. [DOI] [PubMed] [Google Scholar]
  70. Murthy B. S., Sirdeshmukh R. Sensitivity of monomeric and dimeric forms of bovine seminal ribonuclease to human placental ribonuclease inhibitor. Biochem J. 1992 Jan 15;281(Pt 2):343–348. doi: 10.1042/bj2810343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Nenci A., Gotte G., Bertoldi M., Libonati M. Structural properties of trimers and tetramers of ribonuclease A. Protein Sci. 2001 Oct;10(10):2017–2027. doi: 10.1110/ps.14101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Newton D. L., Boque L., Wlodawer A., Huang C. Y., Rybak S. M. Single amino acid substitutions at the N-terminus of a recombinant cytotoxic ribonuclease markedly influence biochemical and biological properties. Biochemistry. 1998 Apr 14;37(15):5173–5183. doi: 10.1021/bi972147h. [DOI] [PubMed] [Google Scholar]
  73. Nogués M. V., Vilanova M., Cuchillo C. M. Bovine pancreatic ribonuclease A as a model of an enzyme with multiple substrate binding sites. Biochim Biophys Acta. 1995 Nov 15;1253(1):16–24. doi: 10.1016/0167-4838(95)00138-k. [DOI] [PubMed] [Google Scholar]
  74. Opitz J. G., Ciglic M. I., Haugg M., Trautwein-Fritz K., Raillard S. A., Jermann T. M., Benner S. A. Origin of the catalytic activity of bovine seminal ribonuclease against double-stranded RNA. Biochemistry. 1998 Mar 24;37(12):4023–4033. doi: 10.1021/bi9722047. [DOI] [PubMed] [Google Scholar]
  75. Palmieri M., Libonati M. Differential, structure-dependent susceptibility of poly(A) and RNA to monomeric and dimeric pancreatic ribonuclease A. Biochim Biophys Acta. 1977 Feb 3;474(3):456–466. doi: 10.1016/0005-2787(77)90274-x. [DOI] [PubMed] [Google Scholar]
  76. Parente A., Palmieri M., De Prisco R., Libonati M. Correlazione fra basicità delle molecole di ribonucleasi e degradazione di RNA a doppia elica: un ulteriore contributo. Boll Soc Ital Biol Sper. 1977 Mar 30;53(6):466–470. [PubMed] [Google Scholar]
  77. Park C., Raines R. T. Dimer formation by a "monomeric" protein. Protein Sci. 2000 Oct;9(10):2026–2033. doi: 10.1110/ps.9.10.2026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Parés X., Nogués M. V., de Llorens R., Cuchillo C. M. Structure and function of ribonuclease A binding subsites. Essays Biochem. 1991;26:89–103. [PubMed] [Google Scholar]
  79. Perutz M. F. Glutamine repeats and neurodegenerative diseases: molecular aspects. Trends Biochem Sci. 1999 Feb;24(2):58–63. doi: 10.1016/s0968-0004(98)01350-4. [DOI] [PubMed] [Google Scholar]
  80. Perutz M. F., Johnson T., Suzuki M., Finch J. T. Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5355–5358. doi: 10.1073/pnas.91.12.5355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Prusiner S. B. Prions. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13363–13383. doi: 10.1073/pnas.95.23.13363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. RICHARDS F. M., VITHAYATHIL P. J. The preparation of subtilisn-modified ribonuclease and the separation of the peptide and protein components. J Biol Chem. 1959 Jun;234(6):1459–1465. [PubMed] [Google Scholar]
  83. Schein C. H. From housekeeper to microsurgeon: the diagnostic and therapeutic potential of ribonucleases. Nat Biotechnol. 1997 Jun;15(6):529–536. doi: 10.1038/nbt0697-529. [DOI] [PubMed] [Google Scholar]
  84. Schmittschmitt Jason P., Scholtz J. Martin. The role of protein stability, solubility, and net charge in amyloid fibril formation. Protein Sci. 2003 Oct;12(10):2374–2378. doi: 10.1110/ps.03152903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Shapiro R. Cytoplasmic ribonuclease inhibitor. Methods Enzymol. 2001;341:611–628. doi: 10.1016/s0076-6879(01)41180-3. [DOI] [PubMed] [Google Scholar]
  86. Shtilerman Mark D., Ding Tomas T., Lansbury Peter T., Jr Molecular crowding accelerates fibrillization of alpha-synuclein: could an increase in the cytoplasmic protein concentration induce Parkinson's disease? Biochemistry. 2002 Mar 26;41(12):3855–3860. doi: 10.1021/bi0120906. [DOI] [PubMed] [Google Scholar]
  87. Sorrentino S., Barone R., Bucci E., Gotte G., Russo N., Libonati M., D'Alessio G. The two dimeric forms of RNase A. FEBS Lett. 2000 Jan 21;466(1):35–39. doi: 10.1016/s0014-5793(99)01742-1. [DOI] [PubMed] [Google Scholar]
  88. Sorrentino S. Human extracellular ribonucleases: multiplicity, molecular diversity and catalytic properties of the major RNase types. Cell Mol Life Sci. 1998 Aug;54(8):785–794. doi: 10.1007/s000180050207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Sorrentino S., Lavitrano M., De Prisco R., Libonati M. Human seminal ribonuclease. A tool to check the role of basic charges and glycosylation of a ribonuclease in the action of the enzyme on double-stranded RNA. Biochim Biophys Acta. 1985 Feb 4;827(2):135–139. doi: 10.1016/0167-4838(85)90081-0. [DOI] [PubMed] [Google Scholar]
  90. Sorrentino S., Libonati M. Human pancreatic-type and nonpancreatic-type ribonucleases: a direct side-by-side comparison of their catalytic properties. Arch Biochem Biophys. 1994 Aug 1;312(2):340–348. doi: 10.1006/abbi.1994.1318. [DOI] [PubMed] [Google Scholar]
  91. Sorrentino S., Libonati M. Structure-function relationships in human ribonucleases: main distinctive features of the major RNase types. FEBS Lett. 1997 Mar 3;404(1):1–5. doi: 10.1016/s0014-5793(97)00086-0. [DOI] [PubMed] [Google Scholar]
  92. Sorrentino Salvatore, Naddeo Mariarosaria, Russo Aniello, D'Alessio Giuseppe. Degradation of double-stranded RNA by human pancreatic ribonuclease: crucial role of noncatalytic basic amino acid residues. Biochemistry. 2003 Sep 2;42(34):10182–10190. doi: 10.1021/bi030040q. [DOI] [PubMed] [Google Scholar]
  93. Soucek J., Matousek J. The binding of bull seminal ribonuclease and its carboxymethylated derivative to human leukaemic cells. Folia Biol (Praha) 1979;25(2):142–144. [PubMed] [Google Scholar]
  94. Taniguchi T., Libonati M. Action of ribonuclease BS-1 on a DNA-RNA hybrid. Biochem Biophys Res Commun. 1974 May 7;58(1):280–286. doi: 10.1016/0006-291x(74)90924-3. [DOI] [PubMed] [Google Scholar]
  95. Tarnowski G. S., Kassel R. L., Mountain I. M., Blackburn P., Wilson G., Wang D. Comparison of antitumor activities of pancreatic ribonuclease and its cross-linked dimer. Cancer Res. 1976 Nov;36(11 Pt 1):4074–4078. [PubMed] [Google Scholar]
  96. Usher D. A., Erenrich E. S., Eckstein F. Geometry of the first step in the action of ribonuclease-A (in-line geometry-uridine2',3'-cyclic thiophosphate- 31 P NMR). Proc Natl Acad Sci U S A. 1972 Jan;69(1):115–118. doi: 10.1073/pnas.69.1.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. VITHAYATHIL P. J., RICHARDS F. M. The reaction of iodoacetate with ribonuclease-S. J Biol Chem. 1961 May;236:1386–1389. [PubMed] [Google Scholar]
  98. Vescia S., Tramontano D., Augusti-Tocco G., D'Alessio G. In vitro studies on selective inhibition of tumor cell growth by seminal ribonuclease. Cancer Res. 1980 Oct;40(10):3740–3744. [PubMed] [Google Scholar]
  99. Wang D., Moore S. Polyspermine-ribonuclease prepared by cross-linkage with dimethyl suberimidate. Biochemistry. 1977 Jun 28;16(13):2937–2942. doi: 10.1021/bi00632a021. [DOI] [PubMed] [Google Scholar]
  100. Wang D., Wilson G., Moore S. Preparation of cross-linked dimers of pancreatic ribonuclease. Biochemistry. 1976 Feb 10;15(3):660–665. doi: 10.1021/bi00648a033. [DOI] [PubMed] [Google Scholar]
  101. Wu Y., Mikulski S. M., Ardelt W., Rybak S. M., Youle R. J. A cytotoxic ribonuclease. Study of the mechanism of onconase cytotoxicity. J Biol Chem. 1993 May 15;268(14):10686–10693. [PubMed] [Google Scholar]
  102. Wu Y., Saxena S. K., Ardelt W., Gadina M., Mikulski S. M., De Lorenzo C., D'Alessio G., Youle R. J. A study of the intracellular routing of cytotoxic ribonucleases. J Biol Chem. 1995 Jul 21;270(29):17476–17481. doi: 10.1074/jbc.270.29.17476. [DOI] [PubMed] [Google Scholar]
  103. Yakovlev G., Moiseyev G. P., Sorrentino S., De Prisco R., Libonati M. Single-strand-preferring RNases degrade double-stranded RNAs by destabilizing its secondary structure. J Biomol Struct Dyn. 1997 Oct;15(2):243–250. doi: 10.1080/07391102.1997.10508189. [DOI] [PubMed] [Google Scholar]
  104. delCardayré S. B., Raines R. T. Structural determinants of enzymatic processivity. Biochemistry. 1994 May 24;33(20):6031–6037. doi: 10.1021/bi00186a001. [DOI] [PubMed] [Google Scholar]

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