Poster abstracts
Poster number 11 submitted by Christian ONeil
Identifying key amino acids differentiating the human and mouse Y145Stop prion protein fibril core structures by solid-state NMR
Christian ONeil (Biophysics), Theint Theint (Department of Chemistry at the Ohio State University)
Abstract:
The conversion of certain α-helical monomers to β-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. By comparing variants of prion protein Y145Stop, we can learn how their differences directly impact the conformation of the fibrils. Solid-state NMR provides high-resolution images that can reveal small structural changes between samples as well as possible heterogeneity within one sample. This technique is used to compare the human and mouse variants of prion protein which have only four sequence mutations near the fibril core. By recording spectra for each mutation, we can determine the role these residues play in the structure of the fibrils. Ultimately, this study will help us identify critical regions along the fibril core that determine its conformation.
References:
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.
T. Theint, Y. Xia, P.S. Nadaud, D. Mukhopadhyay, C.D. Schwieters, K. Surewicz, W.K. Surewicz, C.P. Jaroniec, Structural studies of amyloid fibrils by paramagnetic solid-state nuclear magnetic resonance spectroscopy, J. Am. Chem. Soc. 2018, 140, 13161–13166.
Keywords: prion, nmr, fibril