Poster abstracts
Poster number 16 submitted by Christian ONeil
Identifying key amino acids differentiating the human and mouse Y145Stop prion protein fibril core structures by solid-state NMR
Christian Michael ONeil (Biophysics), Theint Theint (Chemistry)
Abstract:
The conversion of &alpha -helical monomers to &beta -sheet-rich fibrils is determined to be the cause of many neurodegenerative diseases in humans and other animals. To understand how the structure of prion amyloids correspond to the spread and development of these diseases, we first need to study how the primary sequence affects the overall fibril structure. Y145Stop prion protein has been found to be a useful in vitro model to mutate and compare to other animal models that take different fibril morphologies, such as the mouse and Syrian hamster prion protein. Solid-state NMR is the best tool to compare these proteins as it can provide high-resolution images that reveal small structural differences between samples as well as possible heterogeneity within one sample. The goal of this study is to reveal critical residues in the prion protein for fibril formation which could lead to possible treatments for the neurological diseases that they cause.
References:
T. Theint, P.S. Nadaud, K. Surewicz, W.K. Surewicz, C.P. Jaroniec, 13C and 15N chemical shift assignments of mammalian Y145Stop prion protein amyloid fibrils, Biomol. NMR Assign. 2017, 11, 75-80.
T. Theint, P.S. Nadaud, D. Aucoin, J.J. Helmus, S.P. Pondaven, K. Surewicz, W.K. Surewicz, C.P. Jaroniec, Species-dependent structural polymorphism of Y145Stop prion protein amyloid revealed by solid-state NMR spectroscopy, Nat. Commun. 2017, 8, 753.
Bishwajit Kundu, Nilesh R. Maiti, Eric M. Jones, Krystyna A. Surewicz, David L. Vanik, and Witold K. Surewicz, Nucleation-dependent conformational conversion of the Y145Stop variant of human prion protein: Structural clues for prion propagation, PNAS 2003, 100, 21.
Keywords: prion, nmr, fibril