% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Rossetti:201192,
author = {Rossetti, Giulia and Cong, Xiaojing and Caliandro, Rocco
and Legname, Giuseppe and Carloni, Paolo},
title = {{C}ommon {S}tructural {T}raits across {P}athogenic
{M}utants of the {H}uman {P}rion {P}rotein and {T}heir
{I}mplications for {F}amilial {P}rion {D}iseases},
journal = {Journal of molecular biology},
volume = {411},
number = {3},
issn = {0022-2836},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {FZJ-2015-03497},
pages = {700 - 712},
year = {2011},
abstract = {Human (Hu) familial prion diseases are associated with
about 40 point mutations of the gene coding for the prion
protein (PrP). Most of the variants associated with these
mutations are located in the globular domain of the protein.
We performed 50 ns of molecular dynamics for each of these
mutants to investigate their structure in aqueous solution.
Overall, 1.6 μs of molecular dynamics data is presented.
The calculations are based on the AMBER(parm99) force field,
which has been shown to reproduce very accurately the
structural features of the HuPrP wild type and a few
variants for which experimental structural information is
available. The variants present structural determinants
different from those of wild-type HuPrP and the protective
mutation HuPrP(E219K-129M). These include the loss of salt
bridges in α2–α3 regions and the loss of π-stacking
interactions in the β2–α2 loop. In addition, in the
majority of the mutants, the α3 helix is more flexible and
Y169 is more solvent exposed. The presence of similar traits
in this large spectrum of mutations hints to a role of these
fingerprints in their known disease-causing properties.
Overall, the regions most affected by disease-linked
mutations in terms of structure and/or flexibility are those
involved in the pathogenic conversion to the scrapie form of
the protein and in the interaction with cellular partners.
These regions thus emerge as optimal targets for antibody-
and ligand-binding studies.},
cin = {German Research School for Simulation Sciences (GRS) /
IAS-5},
ddc = {570},
cid = {I:(DE-Juel1)GRS-20100316 / I:(DE-Juel1)IAS-5-20120330},
pnm = {899 - ohne Topic (POF2-899)},
pid = {G:(DE-HGF)POF2-899},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000293938500014},
doi = {10.1016/j.jmb.2011.06.008},
url = {https://juser.fz-juelich.de/record/201192},
}