Abstract
The chapter is a straight forward molecular dynamics simulation study of wild-type rabbit prion protein (monomer cellular form) which apparently resists the formation of the scrapie form. The comparison analyses with human and mouse prion proteins done so far show that the rabbit prion protein has a stable structure. The main point is that the enhanced stability of the C-terminal ordered region especially H2 through the D177-R163 salt-bridge formation renders the rabbit prion protein stable. The SB D201-R155 linking H3 and H1 also contributes to the structural stability of rabbit prion protein. The HB H186-R155 partially contributes to the structural stability of rabbit prion protein. Conclusions: Rabbit prion protein was found to own the structural stability, the SBs D177-R163, D201-R155 greatly contribute and the HB H186-R155 partially contributes to this structural stability. These SBs may be important drug targets or they are potentially important drug targets for treating prion diseases. Dima et al. also confirmed this point and pointed out that “correlated mutations that reduce the frustration in the second half of H2 in mammalian prion proteins could inhibit the formation of PrPSc” (Dima and Thirumalai, Biophys J 83(3):1268–1280, 2002; Proc Natl Acad Sci U S A 101(43):15335–15340, 2004).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Case DA, Darden TA, Caldwell JW, Cheatham III TE, Simmerling CL, Wang J, Duke RE, Luo R, Merz KM, Pearlman DA, Crowley M, Walker RC, Zhang W, Wang B, Hayik S, Roitberg A, Seabra G, Wong KF, Paesani F, Wu X, Brozell S, Tsui V, Gohlke H, Yang L, Tan C, Mongan J, Hornak V, Cui G, Beroza P, Mathews DH, Schafmeister C, Ross WS, Kollman PA (2006) AMBER 9, University of California, San Francisco
Case DA, Darden TA, Cheatham TE, Simmerling III CL, Wang J, Duke RE, Luo R, Walker RC, Zhang W, Merz KM, Roberts BP, Wang B, Hayik S, Roitberg A, Seabra G, Kolossváry I, Wong KF, Paesani F, Vanicek J, Liu J, Wu X, Brozell SR, Steinbrecher T, Gohlke H, Cai Q, Ye X, Wang J, Hsieh MJ, Cui G, Roe DR, Mathews DH, Seetin MG, Sagui C, Babin V, Luchko T, Gusarov S, Kovalenko A, Kollman PA (2010) AMBER 11, University of California, San Francisco
Case DA, Pearlman DA, Caldwell JW, Cheatham III TE, Wang J, Ross WS, Simmerling CL, Darden TA, Merz KM, Stanton RV, Cheng AL, Vincent JJ, Crowley M, Tsui V, Gohlke H, Radmer RJ, Duan Y, Pitera J, Massova I, Seibel GL, Singh UC, Weiner PK, Kollman PA (2002) AMBER 7, University of California, San Francisco
Dima RI, Thirumalai D (2002) Exploring the propensities of helices in PrPC to form β sheet using NMR structures and sequence alignments. Biophys J 83(3):1268–1280
Dima RI, Thirumalai D (2004) Probing the instabilities in the dynamics of helical fragments from mouse PrPC. Proc Natl Acad Sci U S A 101(43):15335–15340
El-Bastawissy E, Knaggs MH, Gilbert IH (2001) Molecular dynamics simulations of wild-type and point mutation human prion protein at normal and elevated temperature. J Mol Graph Model 20(2):145–154
Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22(12):2577–2637
Liemann S, Glockshuber R (1999) Influence of amino acid substitutions related to inherited human prion diseases on the thermodynamic stability of the cellular prion protein. Biochemistry 38(11):3258–3267
Mills NL, Surewicz K, Surewicz WK, Sonnichsen FD (2009) Residue 129 polymorphism and conformational dynamics of familial prion diseases associated with the human prion protein variant D178N. doi:10.2210/pdb2k1d/pdb. To be published: http://www.rcsb.org/pdb/explore/explore.do?structureId=2K1D
Riek R, Hornemann S, Wider G, Billeter M, Glockshuber R, Wuthrich K (1996) NMR structure of the mouse prion protein domain PrP(121–231). Nature 382(6587):180–182
Sekijima M, Motono C, Yamasaki S, Kaneko K, Akiyama Y (2003) Molecular dynamics simulation of dimeric and monomeric forms of human prion protein: insight into dynamics and properties. Biophys J 85(2):1176–1185
Shamsir MS, Dalby AR (2005) One gene, two diseases and three conformations: molecular dynamics simulations of mutants of human prion protein at room temperature and elevated temperatures. PROTEINS: Struct Funct Bioinf 59(2):275–290
Vorberg I, Martin HG, Eberhard P, Suzette AP (2003) Multiple amino acid residues within the rabbit prion protein inhibit formation of its abnormal isoform. J Virol 77(3):2003–2009
Wen Y, Li J, Yao WM, Xiong MQ, Hong J, Peng Y, Xiao GF, Lin DH (2010) Unique structural characteristics of the rabbit prion protein. J Biol Chem 285(41):31682–31693
Yang SC, Levine H, Onuchic JN, Cox DL (2005) Structure of infectious prions: stabilization by domain swapping. FASEB J 19(13):1778–1782
Zahn R, Liu AZ, Luhrs T, Riek R, Schroetter CV, Garcia FL, Billeter M, Calzolai L, Wider G, Wuthrich K (2000) NMR solution structure of the human prion protein. Proc Natl Acad Sci U S A 97(1):145–150
Zhang JP, Varghese JN, Epa VC (2006) Studies on the conformational stability of the rabbit prion protein. CSIRO Preventative Health National Research Flagship Science Retreat, Aitken Hill, Melbourne, 12–15 Sept 2006 Poster in Excellence
Zhong LH (2010) Exposure of hydrophobic core in human prion protein pathogenic mutant H187R. J Biomol Struct Dyn 28(3):355–361
Author information
Authors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Zhang, J. (2015). Compared with the NMR Structure and Dynamics of Humans and Mice. In: Molecular Structures and Structural Dynamics of Prion Proteins and Prions. Focus on Structural Biology, vol 9. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-7318-8_4
Download citation
DOI: https://doi.org/10.1007/978-94-017-7318-8_4
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-017-7317-1
Online ISBN: 978-94-017-7318-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)