Abstract
Several amyloid fibrils have cores framed by highly dynamic, intrinsically disordered, domains that can play important roles for function and toxicity. To study these domains in detail using solid-state NMR spectroscopy, site-specific resonance assignments are required. Although the rapid dynamics of these domains lead to considerable averaging of orientation-dependent NMR interactions and thereby line-narrowing, the proton linewidths observed in these samples is far larger than what is regularly observed in solution. Here, we show that it is nevertheless possible to record 3D HNCO, HNCA, and HNcoCA spectra on these intrinsically disordered domains and to obtain site-specific assignments.
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Acknowledgments
The authors thank Tobias Ulmer and Matthias Ernst for fruitful discussions. This work was supported by the University of Southern California, the Whitehall Foundation, and the National Institutes of Health: NIGMS Award R01GM110521.
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Falk, A.S., Siemer, A.B. Dynamic domains of amyloid fibrils can be site-specifically assigned with proton detected 3D NMR spectroscopy. J Biomol NMR 66, 159–162 (2016). https://doi.org/10.1007/s10858-016-0069-2
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DOI: https://doi.org/10.1007/s10858-016-0069-2