Robert Tycko

Robert Tycko

Section Chief
National Institute of Diabetes and Digestive and Kidney Diseases
Bethesda, MD
USA
 301-402-8272
 robertty@mail.nih.gov

Abstract

Insights into Amyloid Formation from Solid State NMR

Amyloid fibril formation by various polypeptides is a biophysically interesting and biomedically important phenomenon, any understanding of which depends on molecular structural information. I will describe my lab’s efforts to elucidate the molecular structures of amyloid-β, Aβ, fibrils, including fibrils that develop in brain tissue of Alzheimer’s disease, AD, patients, primarily using advanced solid state nuclear magnetic resonance, ssNMR, methods. Importantly, Aβ fibrils exhibit self-propagating, molecular-level structural polymorphism, which shows up clearly in ssNMR data as well as in electron microscope images.

Figure 1

Figure 1.Structural models for brain-derived 40-residue amyloid-β fibrils, left, and the core of FUS low-complexity domain fibrils, residues 37-97, developed from ssNMR data, as viewed down the fibril growth direction.

Thus, we are interested in the possibility that structural variations in Aβ fibrils may correlate with variations in severity, progression rate, or other aspects of neurodegeneration in AD. Published data will be reviewed, 1, and more recent data will be presented.

I may also describe our efforts to characterize and understand amyloid fibril formation by low-complexity protein sequences that lack hydrophobic residues, especially the low-complexity domain of the FUS protein. 2 In this case, major mysteries surround the nature of interactions that drive amyloid formation, which we are currently addressing by ssNMR experiments.

Authors

Robert Tycko

Affiliations

Laboratory of Chemical Physics, NIDDK

Citations

1. Qiang et al., Nature 541, 217-221, 2017
2. Murray et al., Cell 171, 615-627, 2017

Lecture Images

Robert Tycko presenting at APS2019 Robert Tycko presenting at APS2019 Robert Tycko presenting at APS2019