[NMR paper] Modeling an in-register, parallel "iowa" a? fibril structure using solid-state NMR data from labeled samples with rosetta.

[nmrlearner]

Modeling an in-register, parallel "iowa" a? fibril structure using solid-state NMR data from labeled samples with rosetta.

Related Articles Modeling an in-register, parallel "iowa" a? fibril structure using solid-state NMR data from labeled samples with rosetta.

Structure. 2015 Jan 6;23(1):216-27

Authors: Sgourakis NG, Yau WM, Qiang W

Abstract
Determining the structures of amyloid fibrils is an important first step toward understanding the molecular basis of neurodegenerative diseases. For ?-amyloid (A?) fibrils, conventional solid-state NMR structure determination using uniform labeling is limited by extensive peak overlap. We describe the characterization of a distinct structural polymorph of A? using solid-state NMR, transmission electron microscopy (TEM), and Rosetta model building. First, the overall fibril arrangement is established using mass-per-length measurements from TEM. Then, the fibril backbone arrangement, stacking registry, and "steric zipper" core interactions are determined using a number of solid-state NMR techniques on sparsely (13)C-labeled samples. Finally, we perform Rosetta structure calculations with an explicitly symmetric representation of the system. We demonstrate the power of the hybrid Rosetta/NMR approach by modeling the in-register, parallel "Iowa" mutant (D23N) at high resolution (1.2Å backbone rmsd). The final models are validated using an independent set of NMR experiments that confirm key features.


PMID: 25543257 [PubMed - indexed for MEDLINE]



More...