Abstract
Replica exchange molecular dynamics simulations in neutral and acidic aqueous solutions were employed to study the intrinsic helical propensities of three helices in both Syrian hamster (syPrP) and human (huPrP) prion proteins. The helical propensities of syPrP HA and huPrP HA are very high under both pH conditions, which implies that HA is barely involved in the helix-to-β transition. The SyPrP HB chain has a strong tendency to adopt an extended conformation, which is possibly involved in the mechanism of infectious prion diseases in Syrian hamster. HuPrP HC has more of a preference for the extended conformation than huPrP HA and huPrP HB do, which leads to the conjecture that it is more likely to be the source of β-rich structure for human prion protein. We also noticed that the presence of salt bridges is not correlated with helical propensity, indicating that salt bridges do not stabilize helices.
Similar content being viewed by others
References
Prusiner SB (1998) Proc Natl Acad Sci USA 95:13363
Caughey B (2003) Br Med Bull 66:109
Mastrianni JA (2004) Clin Neurosci Res 3:469
Millhauser GL (2007) Copper and the prion protein: methods, structures, function, and disease. In: Annual review of physical chemistry, vol 58. Annual Reviews, Palo Alto, p 299
Khan MQ, Sweeting B, Mulligan VK, Arslan PE, Cashman NR, Pai EF, Chakrabartty A (2010) Proc Natl Acad Sci USA 107:19808
Gibbs CJ Jr, Gajdusek DC (1973) Science 182:67
Thomzig A, Cardone F, Kruger D, Pocchiari M, Brown P, Beekes M (2006) J Gen Virol 87:251
Kimberlin RH, Walker C (1977) J Gen Virol 34:295
Bessen RA, Marsh RF (1992) J Gen Virol 73(Pt 2):329
Lasmezas CI, Deslys JP, Robain O, Jaegly A, Beringue V, Peyrin JM, Fournier JG, Hauw JJ, Rossier J, Dormont D (1997) Science 275:402
Chandler RL (1961) Lancet 1:1378
Hill AF, Joiner S, Linehan J, Desbruslais M, Lantos PL, Collinge J (2000) Proc Natl Acad Sci USA 97:10248
Barlow RM, Rennie JC (1976) Res Vet Sci 21:110
Chianini F, Fernández-Borges N, Vidal E, Gibbard L, Pintado B, de Castro J, Priola SA, Hamilton S, Eaton SL, Finlayson J, Pang Y, Steele P, Reid HW, Dagleish MP, Castilla J (2012) Proc Natl Acad Sci USA 109:5080
Pan KM, Baldwin M, Nguyen J, Gasset M, Serban A, Groth D, Mehlhorn I, Huang Z, Fletterick RJ, Cohen FE (1993) Proc Natl Acad Sci USA 90:10962
Sunde M, Serpell LC, Bartlam M, Fraser PE, Pepys MB, Blake CCF (1997) J Mol Biol 273:729
Cobb NJ, Sonnichsen FD, McHaourab H, Surewicz WK (2007) Proc Natl Acad Sci USA 104:18946
Lu XJ, Wintrode PL, Surewicz WK (2007) Proc Natl Acad Sci USA 104:1510
Swietnicki W, Morillas M, Chen SG, Gambetti P, Surewicz WK (2000) Biochemistry 39:424
Morillas M, Vanik DL, Surewicz WK (2001) Biochemistry 40:6982
Cobb NJ, Apetri AC, Surewicz WK (2008) J Biol Chem 283:34704
Wuthrich K, Riek R (2001) Adv Protein Chem 57:55
Harris DA (1999) Clin Microbiol Rev 12:429
Prusiner SB, McKinley MP, Bowman KA, Bolton DC, Bendheim PE, Groth DF, Glenner GG (1983) Cell 35:349
Abid K, Soto C (2006) Cell Mol Life Sci 63:2342
Cobb NJ, Surewicz WK (2009) Biochemistry 48:2574
Nguyen JT, Inouye H, Baldwin MA, Fletterick RJ, Cohen FE, Prusiner SB, Kirschner DA (1995) J Mol Biol 252:412
Jackson GS, Hill SF, Joseph C, Hosszu L, Power A, Waltho JP, Clarke AR, Collinge J (1999) Biochim Biophys Acta Protein Struct Mol Enzymol 1431:1
Caughey BW, Dong A, Bhat KS, Ernst D, Hayes SF, Caughey WS (1991) Biochemistry 30:7672
Swietnicki W, Petersen R, Gambetti P, Surewicz WK (1997) J Biol Chem 272:27517
Hornemann S, Glockshuber R (1998) Proc Natl Acad Sci USA 95:6010
DeMarco ML, Daggett VCR (2005) Biol 328:847
DeMarco ML, Silveira J, Caughey B, Daggett V (2006) Biochemistry 45:15573
DeMarco ML, Daggett V (2004) Proc Natl Acad Sci USA 101:2293
Ding F, LaRocque JJ, Dokholyan NV (2005) J Biol Chem 280:40235
Dima RI, Thirumalai D (2004) Proc Natl Acad Sci USA 101:15335
Langella E, Improta R, Barone V (2004) Biophys J 87:3623
De Simone A, Dodson GG, Verma CS, Zagari A, Fraternali F (2005) Proc Natl Acad Sci USA 102:7535
De Simone A, Zagari A, Derreumaux P (2007) Biophys J 93:1284
Langella E, Improta R, Crescenzi O, Barone V (2006) Proteins 64:167
Gu W, Wang TT, Zhu J, Shi YY, Liu HY (2003) Biophys Chem 104:79
Barducci A, Chelli R, Procacci P, Schettino V (2005) Biophys J 88:1334
Sekijima M, Motono C, Yamasaki S, Kaneko K, Akiyama Y (2003) Biophys J 85:1176
Shamsir MS, Dalby AR (2005) Proteins 59:275
Shamsir MS, Dalby AR (2007) Biophys J 92:2080
van der Kamp MW, Daggett V (2010) Biophys J 99:2289
Campos SRR, Machuqueiro M, Baptista AM (2010) J Phys Chem B 114:12692
Alonso DOV, DeArmond SJ, Cohen FE, Daggett V (2001) Proc Natl Acad Sci USA 98:2985
Vila-Vicosa D, Campos SRR, Baptista AM, Machuqueiro M (2012) J Phys Chem B 116:8812
Hornemann S, Korth C, Oesch B, Riek R, Wider G, Wuthrich K, Glockshuber R (1997) FEBS Lett 413:277
Norstrom EM, Mastrianni JA (2006) J Virol 80:8521
Wille H, Michelitsch MD, Guenebaut V, Supattapone S, Serban A, Cohen FE, Agard DA, Prusiner SB (2002) Proc Natl Acad Sci USA 99:3563
Hansmann UHE, Okamoto Y (1999) Curr Opin Struct Biol 9:177
Mitsutake A, Sugita Y, Okamoto Y (2001) Biopolymers 60:96
Sugita Y, Okamoto Y (1999) Chem Phys Lett 314:141
Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, Simmerling C (2006) Proteins 65:712
Onufriev A, Bashford D, Case DA (2004) Proteins 55:383
Ryckaert JP, Ciccotti G, Berendsen HJC (1977) J Comput Phys 23:327
Kumar S, Bouzida D, Swendsen RH, Kollman PA, Rosenberg JM (1992) J Comput Chem 13:1011
Chodera JD, Swope WC, Pitera JW, Seok C, Dill KA (2007) J Chem Theory Comput 3:26
Ziegler J, Sticht H, Marx UC, Muller W, Rosch P, Schwarzinger S (2003) J Biol Chem 278:50175
Chen J, Thirumalai D (2012) Biochemistry 52:310
Acknowledgments
We are grateful for the financial support from the National Natural Science Foundation of China (grant nos. 10974054, 20933002, and 21173082). We also thank Prof. Donghai Lin and Dr. Yi Wen at Xiamen University for helpful discussions. The High Performance Computer Center of East China Normal University is acknowledged for its support in allowing us CPU time.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lu, X., Zeng, J., Gao, Y. et al. The intrinsic helical propensities of the helical fragments in prion protein under neutral and low pH conditions: a replica exchange molecular dynamics study. J Mol Model 19, 4897–4908 (2013). https://doi.org/10.1007/s00894-013-1985-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00894-013-1985-7