Mechanistic prospective for human PrPC conversion to PrPSc: Molecular dynamic insights | ||
| Molecular Biology Research Communications | ||
| مقاله 1، دوره 2، شماره 4، اسفند 2013، صفحه 109-122 اصل مقاله (965.98 K) | ||
| نوع مقاله: Original article | ||
| شناسه دیجیتال (DOI): 10.22099/mbrc.2013.1819 | ||
| نویسندگان | ||
| Nooshin Azari1؛ Mohammad Reza Dayer* 2؛ Nematollah Razmi3؛ Mohammad Saaid Dayer4 | ||
| 1Biochemistry Department, Basic Sciences, Fars Science& Research Branch, Islamic Azad University, Shiraz, Islamic Republic of Iran | ||
| 2Department of Biology, Faculty of Science, Shahid Chamran University, Ahvaz, Iran | ||
| 3Biochemistry Department, Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Islamic Republic of Iran | ||
| 4Department of Parasitology and Medical Entomology, Tarbiat Modares University, Tehran, Islamic Republic of Iran | ||
| چکیده | ||
| PrPC conversion to PrPSc isoform is the main known cause for prion diseases including Crutzfeldt-Jakob, Gerstmann-Sträussler-Sheinker syndrome and fatal familial insomnia in human. The precise mechanism underling this conversion is yet to be well understood. In the present work, using the coordinate file of PrPC (available on the Protein Data Bank) as a starting structure, separate molecular dynamic simulations were carried out at neutral and acidic pH in an explicit water box at 37°C and 1 atmosphere pressure for 10ns second period. Results showed that the acidic pH accelerates PrPC conversion to PrPSc by decreasing the protein gyration radius, flexibility and protein-solvent hydrogen bonds. In acidic conditions, PrPC attains a more folded and less flexible tertiary structure compared to its native structure at neutral pH; otherwise, the decrease of protein-solvent hydrogen bonds at acidic pH will enhance the hydrophobic character of PrPC that may exhibit association as multimeric assemblies. It can also lower water solubility and increase resistance to proteolytic degradations. Data indicated that there was no sensible protein denaturation during this conversion. It is hypothesized that the formation of slightly misfolded conformations with minor structural changes in secondary and/or tertiary structures are enough to menace scrapie formation in PrPC. Our findings show that scrapie formation seems to be a theoretically reversible process. | ||
| کلیدواژهها | ||
| Human Prion Protein؛ Prion Disease؛ pH؛ Misfolded Structure؛ Molecular Dynamic Simulation | ||
| مراجع | ||
|
1.Chesebro B, Race R, Wehrly K, Nishio J, Bloom M, Lechner D, Bergstrom S, Robbins K, Mayer L, Keith JM, Garon C, Haase A. Identification of scrapie prion protein-specific mrna in scrapie-infected and uninfected brain. Nature 1985;315:331-333.
2.Basler K, Oesch B, Scott M, Westaway D, Walchli M, Groth DF, McKinley MP, Prusiner SB, Weissmann C. Scrapie and cellular prp isoforms are encoded by the same chromosomal gene. Cell 1986;46:417-428.
3.Sparkes RS, Simon M, Cohn VH, Fournier RE, Lem J, Klisak I, Heinzmann C, Blatt C, Lucero M, Mohandas T, DeArmond SJ, Westaway D, Prusiner SB, Weiner LP. Assignment of the human and mouse prion protein genes to homologous chromosomes. Proc Natl Acad Sci USA 1986;83:7358-7362.
4.Linden R, Martins VR, Prado MA, Cammarota M, Izquierdo I, Brentani RR. Physiology of the prion protein. Physiol Rev 2008;88:673-728.
5.Zahn R, Liu A, Luhrs T, Riek R, von Schroetter C, López García F, Billeter M, Calzolai L, Wide G, Wuthrich K. NMR solution structure of the human prion protein. Proc Natl Acad Sci USA 2000; 97:145–150.
6.Moore RA, Taubner LM, Priola SA. Prion protein misfolding and disease. Curr Opin Struct Biol 2009;19:14-22.
7.Viles JH, Cohen FE, Prusiner SB, Goodin DB, Wright PE, Dyson HJ. Copper binding to the prion protein: structural implications of four identical cooperative binding sites. Proc Natl Acad Sci USA 1999;96:2042-2047.
8.Whittal RM, Ball HL, Cohen FE, Burlingame AL, Prusiner SB, Baldwin MA. Copper binding to octarepeat peptides of the prion protein monitored by mass spectrometry. Protein Science 2000; 9:332–343.
9.Morillas M, Swietnicki W, Gambetti P, Surewicz WK. Membrane environment alters the conformational structure of the recombinant human prion protein. J Biol Chem 1999;4:36859-36865.
10.Stahl N, Borchelt DR, Hsiao K, Prusiner SB. Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell 1987;51:229-240.
11.Stahl N, Baldvin MA, Hecker R, Pan KM, Burlingame AL, Prusiner SB. Glycosylinositol phospholipid anchors of the scrapie and cellular prion proteins contain sialic acid. Biochemistry 1992;31:5043-5053.
12.Chen J, Thirumalai D. Helices 2 and 3 are the initiation sites in the PrPC → PrPSc transition. Biochemistry 2013;52:310-319.
13.Mouillet-Richard S, Ermonval M, Chebassier C, Laplanche JL, Lehmann S, Launay JM, Kellermann O. Signal transduction through prion protein. Science 2000;289:1925-1928.
14.Linden R, Cordeiro Y, Lima LM. Allosteric function and dysfunction of the prion protein. Cell Mol Life Sci 2012;69:1105-1124.
15.Gibbings D, Leblanc P, Jay F, Pontier D, Michel F, Schwab, Y, Alais S, Lagrange T, Voinnet O. Human prion protein binds argonaute and promotes accumulation of microrna effector complexes. Nat Struct Mol Biol 2012;19:517-524.
16.Borchelt DR, Rogers M, Stahl N, Telling G, Prusiner SB. Release of the cellular prion protein from cultured cells after loss of its glycoinositol phospholipid anchor. Glycobiology 1993;3:319-329.
17.Starke R, Harrison P, Drummond O, Macgregor I, Mackie I, Machin S. The majority of cellular prion protein released from endothelial cells is soluble. Transfusion 2003;43: 677-678.
18.Meyer RK, McKinley MP, Bowman KA, Braunfeld MB, Barry RA, Prusiner SB. Separation and properties of cellular and scrapie prion proteins. Proc Natl Acad Sci USA 1986;83:2310-2314.
19.Pan KM, Baldwin M, Nguyen J, Gasset M, Serban A, Groth D, Mehlhorn I, Huang Z, Fletterick RJ, Cohen FE, Prusiner SB. Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci USA 1993; 90:10962-10966.
20.Stahl N, Baldwin MA, Teplow DB, Hood L, Gibson BW, Burlingame AL, Prusiner SB. Structural studies of the scrapie prion protein using mass spectrometry and amino acid sequencing. Biochemistry 1993;32:1991-2002.
21.Prusiner SB. Prions. Proc Natl Acad Sci USA 1998;95:13363-13383.
22.Prusiner SB, DeArmond SJ. Biology and genetics of prion diseases. Annu Rev Neurosci 1994;17:311-319.
23.DeArmond SJ, Prusiner SB. Etiology and pathogenesis of prion diseases. Am J Pathol 1995;146:785-811.
24.Griffith JS. Self-replication and scrapie. Nature 1967;215:1043-1044.
25.Come JH, Fraser PE, Lansbury PT Jr. A kinetic model for amyloid formation in the prion diseases: importance of seeding. Proc Natl Acad Sci USA 1993;90:5959-5963.
26.Collinge J, Clarke AR. A general model of prion strains and their pathogenicity. Science 2007;318:930-936.
27.Caughey B, Baron GS. Prions and their partners in crime. Nature 2006;443:803-810.
28.Cobb NJ, Surewicz WK. Prion diseases and their biochemical mechanisms. Biochemistry 2009;48:2574-2585.
29.Horiuchi M, Caughey B. Prion protein interconversions and the transmissible spongiform encephalopathies. Structure 1999;7:R231-R240.
30.Tompa P, Tusnady GE, Simon I. The role of dimerization in prion replication. Biophys J 2002; 82:1711–1718
31.Caughey B, Baron GS, Chesebro B, Jeffrey M. Getting a grip on prions: oligomers, amyloids, and pathological membrane interactions. Annu Rev Biochem 2009;78:177-204.
32.Borchelt DR, Taraboulos A, Prusiner SB. Evidence for synthesis of scrapie prion proteins in the endocytic pathway. J Biol Chem 1992;267:16188-16199.
33.Taraboulos A, Serban D, Prusiner SB. Scrapie prion proteins accumulate in the cytoplasm of persistently infected cultured cells. J Cell Biol 1990;110:2117-2132.
34.Zou WQ, Cashman NR. Acidic pH and detergents enhance in vitro conversion of human brain PrPC to PrPSc -like form. J Biol Chem 2002;277:43492-43947.
35.Calzolai L, Zahn R. Influence of pH on NMR structure and stability of the human prion protein blobular domain. J Biol Chem 2003;278:35592-35596.
36.DeMarco ML, Daggett V. From conversion to aggregation: protoWbril formation of the prion protein. Proc Natl Acad Sci USA 2004;101:2293-2298.
37.Stiffin RM, Sullivan SM, Carlson GM, Holyoak T. Differential inhibition of cytosolic PEPCK by substrate analogues. Kinetic and structural characterization of inhibitor recognition. Biochemistry 2008;47:2099-2109.
38.Lee B, Richards FM. The interpretation of protein structures: estimation of static accessibility. J Mol Biol 1971;55:379-400.
39.Baker WR, Kintanar A. Characterization of the pH titration shifts of ribonuclease A by one- and two-dimensional nuclear magnetic resonance spectroscopy. Arch Biochem Biophys 1996;327:189-199.
40.Peters GH, van Aalten DM, Svendsen A, Bywater R. Essential dynamics of lipase binding sites: the effect of inhibitors of different chain length. Protein Eng 1997;10: 149-158. | ||
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