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Constructing a 3‐D Molecular Model to Highlight the Conversion of the Normal Protein PrP C into the Mutated PrP SC in a Prion Disease
Author(s) -
Schmitt Lavin Emily F.,
Barraza Allan,
Bui Hoang Gwen,
Speth Robert
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.lb205
Subject(s) - protein data bank (rcsb pdb) , protein data bank , protein structure , mutation , biology , chemistry , computational biology , gene , genetics , biochemistry
Gerstmann‐Straussler‐Scheinker (GSS) is a rare, genetically inherited prion disease caused by a mutation in the prion protein gene (PRNP). Patients who are carriers begin to experience GSS symptoms (similar to Parkinson's and Alzheimer's) during their 30s and 40s. This prion protein was modeled to reflect the changes in protein structure that leads to this disorder. While molecular details concerning the progression of this condition remain largely unknown, the alteration in shape of the prion protein could be directly involved in the aggregation of plaques contributing to the progression of GSS. The Milwaukee School of Engineering (MSOE) Center for Biomolecular Modeling ‐ Students Modeling A Research Topic (CBM‐SMART) team at Nova Southeastern University used 3‐D modeling and printing technology to examine structure and function relationships between this normal and mutated prion protein. Details of the normal GSS prion structure (PrP C ) from the Protein Data Bank (PDB) File, 3HAK, were imported into Jmol, a protein visualization software. Next, the mutated form of the GSS prion protein, PrP SC (PDB file 3HER) was imported into Jmol. The differences between the two proteins were studied. Jmol commands were used to highlight these differences and a 3‐D molecular model was printed to explain the transition from normal to mutated protein. The transitions highlighted included a mutation in which phenylalanine becomes serine at positon 198, a loop from residues 193–197 which becomes deleted, and the alpha helix structure at residues 164 – 170 which becomes malformed due to the formation of a salt bridge between arginine 164 and aspartic acid 167. The N‐ and C‐ termini of the prion protein were also highlighted. This model can be used by genetic counselors, physicians, and researchers to educate the public on the molecular changes associated with prion diseases like GSS. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .