Abstract
Human prion diseases include CJDs, FFI, GSS, and kuru. It is very necessary to MD study the NMR structures of human prion proteins. We found the NMR structures are in two classes: produced at pH 4.5, and produced at 7.0 – they have same global fold but also have slight but strict local differences. This chapter does MD studies on the pH 4.5 Structure (PDB entry 1QLX) and the pH 7.0 Structures (PDB entries 1HJM, 1HJN). We found in PrP structures, wild-type human dimer (with M/V129) has the unique domain-swapping crystal structures. The structure has the three-dimensional swapping of α-helix 3 and a rearrangement of the disulfide bond. Some regions of familial prion disease mutations exactly map onto the α-helix 3 swapped. This chapter will also do MD studies on the crystal structures of the dimer (PDB entry 1I4M) and its M129V mutant (PDB entries 3HJ5, 3HAF).
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References
Calzolai L, Zahn R (2003) Influence of pH on NMR structure and stability of the human prion protein globular domain. J Biol Chem 278(37):35592–35596
Knaus KJ, Morillas M, Swietnicki W, Malone M, Surewicz WK, Yee VC (2001) Crystal structure of the human prion protein reveals a mechanism for oligomerization. Nat Struct Biol 8(9): 770–774
Lee S, Antony L, Hartmann R, Knaus KJ, Surewicz K, Surewicz WK, Yee VC (2010) Conformational diversity in prion protein variants influences intermolecular β-sheet formation. EMBO J 29(1):251–262
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 USA 97(1):145–150
Zhang JP (2011c) Comparison studies of the structural stability of rabbit prion protein with human and mouse prion proteins. J Theor Biol 269(1):88–95
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Zhang, J. (2018). Human PrPC Monomer, Dimer and Its M129V Mutant. In: Molecular Dynamics Analyses of Prion Protein Structures. Focus on Structural Biology, vol 10. Springer, Singapore. https://doi.org/10.1007/978-981-10-8815-5_11
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DOI: https://doi.org/10.1007/978-981-10-8815-5_11
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