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), 327-340. (doi: 10.1002/(SICI)1097-0134(20000215)38:3<327::AID-PROT8>3.0.CO;2-G).

Download

Full text not available from this repository.

Description/Abstract

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
Related URLs:
Keywords: computer simulation, prion, conformational flexibility, digital filter, mutantscreutzfeldt-jakob-disease, prion protein, scrapie prion, collectivemotions, trajectories, simulations, conversion, isoform
Subjects: Q Science
Q Science > QD Chemistry
Divisions: University Structure - Pre August 2011 > School of Chemistry
ePrint ID: 18962
Date Deposited: 19 Jan 2006
Last Modified: 27 Mar 2014 18:08
URI: http://eprints.soton.ac.uk/id/eprint/18962

Actions (login required)

View Item View Item