TY - JOUR
T1 - Exposure of hydrophobic core in human prion protein pathogenic mutant h187r
AU - Zhong, Linghao
N1 - Funding Information:
We thank Professor John Brady for encouraging this work. This research was supported by the Pennsylvania State University High Performance Computing (HPC) Group.
Funding Information:
This work was supported in part through instrumentation funded by the National Science Foundation through grant OCI-0821527.
PY - 2010/12
Y1 - 2010/12
N2 - Pathogenesis studies have revealed that H187R mutation of human prion protein (huPrP) is related to GSS type of TSE diseases. Its pathogenic mechanism is still unclear. We here studied the globular domain of this mutant protein by molecular dynamics simulations. Compared to the wide-type protein, the mutant has similar dynamics and stability profiles in our simulation. Conformational rearrangements are concentrated around the mutation site, due to the introduction the positively charged side chain of Arg187. The strong electrostatic repulsion between Arg156 and Arg187 drives both side chains away from their original positions, leaving its hydrophobic core to be solvent accessible. Such a unfavorable conformational change may destabilize the mutant protein and make it more susceptible to unfolding.
AB - Pathogenesis studies have revealed that H187R mutation of human prion protein (huPrP) is related to GSS type of TSE diseases. Its pathogenic mechanism is still unclear. We here studied the globular domain of this mutant protein by molecular dynamics simulations. Compared to the wide-type protein, the mutant has similar dynamics and stability profiles in our simulation. Conformational rearrangements are concentrated around the mutation site, due to the introduction the positively charged side chain of Arg187. The strong electrostatic repulsion between Arg156 and Arg187 drives both side chains away from their original positions, leaving its hydrophobic core to be solvent accessible. Such a unfavorable conformational change may destabilize the mutant protein and make it more susceptible to unfolding.
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U2 - 10.1080/07391102.2010.10507365
DO - 10.1080/07391102.2010.10507365
M3 - Article
C2 - 20919751
AN - SCOPUS:78649855154
SN - 0739-1102
VL - 28
SP - 355
EP - 361
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
IS - 3
ER -
