The Intrinsic Helical Propensities of the Helical Fragments in Prion Protein Under Neutral and Low PH Conditions: a Replica Exchange Molecular Dynamics Study

Overview

Journal J Mol Model

Publisher Springer

Specialty Molecular Biology

Date 2013 Sep 18

PMID 24043543

Citations 3

Authors

Xiaoliang Lu

Juan Zeng

Ya Gao

John Z H Zhang

Dawei Zhang

Ye Mei

Affiliations

Soon will be listed here.

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.

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References

Lu X, Wintrode P, Surewicz W . Beta-sheet core of human prion protein amyloid fibrils as determined by hydrogen/deuterium exchange. Proc Natl Acad Sci U S A. 2007; 104(5):1510-5. PMC: 1785245. DOI: 10.1073/pnas.0608447104. View

Lasmezas C, Deslys J, Robain O, Jaegly A, Beringue V, Peyrin J . Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein. Science. 1997; 275(5298):402-5. DOI: 10.1126/science.275.5298.402. View

De Simone A, Zagari A, Derreumaux P . Structural and hydration properties of the partially unfolded states of the prion protein. Biophys J. 2007; 93(4):1284-92. PMC: 1929054. DOI: 10.1529/biophysj.107.108613. View

Kimberlin R, Walker C . Characteristics of a short incubation model of scrapie in the golden hamster. J Gen Virol. 1977; 34(2):295-304. DOI: 10.1099/0022-1317-34-2-295. View

Wille H, Michelitsch M, Guenebaut V, Supattapone S, Serban A, Cohen F . Structural studies of the scrapie prion protein by electron crystallography. Proc Natl Acad Sci U S A. 2002; 99(6):3563-8. PMC: 122563. DOI: 10.1073/pnas.052703499. View

Mitsutake A, Sugita Y, Okamoto Y . Generalized-ensemble algorithms for molecular simulations of biopolymers. Biopolymers. 2001; 60(2):96-123. DOI: 10.1002/1097-0282(2001)60:2<96::AID-BIP1007>3.0.CO;2-F. View

Langella E, Improta R, Barone V . Checking the pH-induced conformational transition of prion protein by molecular dynamics simulations: effect of protonation of histidine residues. Biophys J. 2004; 87(6):3623-32. PMC: 1304876. DOI: 10.1529/biophysj.104.043448. View

Khan M, Sweeting B, Mulligan V, Arslan P, Cashman N, Pai E . Prion disease susceptibility is affected by beta-structure folding propensity and local side-chain interactions in PrP. Proc Natl Acad Sci U S A. 2010; 107(46):19808-13. PMC: 2993331. DOI: 10.1073/pnas.1005267107. View

Onufriev A, Bashford D, Case D . Exploring protein native states and large-scale conformational changes with a modified generalized born model. Proteins. 2004; 55(2):383-94. DOI: 10.1002/prot.20033. View

10.

CHANDLER R . Encephalopathy in mice produced by inoculation with scrapie brain material. Lancet. 1961; 1(7191):1378-9. DOI: 10.1016/s0140-6736(61)92008-6. View

11.

Thomzig A, Cardone F, Kruger D, Pocchiari M, Brown P, Beekes M . Pathological prion protein in muscles of hamsters and mice infected with rodent-adapted BSE or vCJD. J Gen Virol. 2005; 87(Pt 1):251-254. DOI: 10.1099/vir.0.81277-0. View

12.

Shamsir M, Dalby A . Beta-sheet containment by flanking prolines: molecular dynamic simulations of the inhibition of beta-sheet elongation by proline residues in human prion protein. Biophys J. 2006; 92(6):2080-9. PMC: 1861792. DOI: 10.1529/biophysj.106.092320. View

13.

Ding F, LaRocque J, Dokholyan N . Direct observation of protein folding, aggregation, and a prion-like conformational conversion. J Biol Chem. 2005; 280(48):40235-40. DOI: 10.1074/jbc.M506372200. View

14.

Sekijima M, Motono C, Yamasaki S, Kaneko K, Akiyama Y . Molecular dynamics simulation of dimeric and monomeric forms of human prion protein: insight into dynamics and properties. Biophys J. 2003; 85(2):1176-85. PMC: 1303235. DOI: 10.1016/S0006-3495(03)74553-6. View

15.

De Simone A, Dodson G, Verma C, Zagari A, Fraternali F . Prion and water: tight and dynamical hydration sites have a key role in structural stability. Proc Natl Acad Sci U S A. 2005; 102(21):7535-40. PMC: 1140432. DOI: 10.1073/pnas.0501748102. View

16.

Abid K, Soto C . The intriguing prion disorders. Cell Mol Life Sci. 2006; 63(19-20):2342-51. PMC: 2804267. DOI: 10.1007/s00018-006-6140-5. View

17.

Morillas M, Vanik D, Surewicz W . On the mechanism of alpha-helix to beta-sheet transition in the recombinant prion protein. Biochemistry. 2001; 40(23):6982-7. DOI: 10.1021/bi010232q. View

18.

Gibbs Jr C, Gajdusek D . Experimental subacute spongiform virus encephalopathies in primates and other laboratory animals. Science. 1973; 182(4107):67-8. DOI: 10.1126/science.182.4107.67. View

19.

Vila-Vicosa D, Campos S, Baptista A, Machuqueiro M . Reversibility of prion misfolding: insights from constant-pH molecular dynamics simulations. J Phys Chem B. 2012; 116(30):8812-21. DOI: 10.1021/jp3034837. View

20.

Nguyen J, Inouye H, Baldwin M, Fletterick R, Cohen F, Prusiner S . X-ray diffraction of scrapie prion rods and PrP peptides. J Mol Biol. 1995; 252(4):412-22. DOI: 10.1006/jmbi.1995.0507. View