Expression and purification of a recombinant amyloidogenic peptide from transthyretin for solid-state NMR spectroscopy

We describe the expression and purification of a model amyloidogenic peptide comprising residues 105–115 of human transthyretin (TTR105–115). Recombinant TTR105–115, which does not contain any non-native residues, was prepared as part of a fusion protein construct with a highly soluble B1 immunoglobulin binding domain of protein G (GB1), with typical yields of ∼4 mg/L of uniformly 13C,15N-enriched HPLC-purified peptide per liter of minimal media culture. Amyloid fibrils formed by recombinant TTR105–115 were characterized by transmission electron microscopy and solid-state NMR spectroscopy, and found to be comparable to synthetic TTR105–115 fibrils. These results establish recombinant TTR105–115 as a valuable model system for the development of new solid-state NMR techniques for the atomic-level characterization of amyloid architecture.