Molecular dynamics of mouse and syrian hamster PrP: Implications for activity

Parchment, O. G. and Essex, J. W. (2000) Molecular dynamics of mouse and syrian hamster PrP: Implications for activity Proteins-Structure Function and Genetics, 38, (3), pp. 327-340. (doi:10.1002/(SICI)1097-0134(20000215)38:3<327::AID-PROT8>3.0.CO;2-G).


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Molecular dynamics computer simulations have been performed on Mouse (Mo) and Syrian Hamster (SHa) prion proteins. These proteins differ, primarily, in that the SHa form incorporates additional residues at the C-terminus and also includes a segment of the unstructured N-terminal region that is required for infectivity, The 1-ns simulations have been analyzed by using a combination of dynamical cross-correlation maps, residue-residue contact plots, digital filtering, and residue-based root-mean-square deviations. The results show that the extra residues present in the SHa form at the C- and N-termini produce changes in the stability of key regions of the protein. The loop region between strand S2 and helix B that contains part of the proposed discontinuous binding site for the chaperone, protein X, is found to be more stable in SHa than in the Mo protein; these results are consistent with the NMR data of James et al, (James et al, Proc Natl Acad Sci USA 1997;94:10086-10091), In addition, a degree of flexibility within the region between and including strand S1 and helix A is also shown in SHa, which is not present in the Mo form; the cross-correlation maps suggest that this is a consequence of the additional unstructured N-terminal region. Furthermore, the extra residues in the N-terminal region of SHa are found to form a beta-bridge with the beta-sheet, within which critical point mutations associated with prion diseases lie. The implications of these results for the conformational interconversion pathway of the prion protein are discussed.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1002/(SICI)1097-0134(20000215)38:3<327::AID-PROT8>3.0.CO;2-G
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Keywords: computer simulation, prion, conformational flexibility, digital filter, mutantscreutzfeldt-jakob-disease, prion protein, scrapie prion, collectivemotions, trajectories, simulations, conversion, isoform
ePrint ID: 18962
Date :
Date Event
15 February 2000Published
Date Deposited: 19 Jan 2006
Last Modified: 16 Apr 2017 23:07
Further Information:Google Scholar

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