Untangling a Repetitive Amyloid Sequence: Correlating Biofilm-Derived and Segmentally Labeled Curli Fimbriae by Solid-State NMR Spectroscopy

Curli are functional bacterial amyloids produced by an intricate biogenesis machinery. Insights into their folding and regulation can advance our understanding of amyloidogenesis. However, gaining detailed structural information of amyloids, and their tendency for structural polymorphisms, remains challenging. Herein we compare high‐quality solid‐state NMR spectra from biofilm‐derived and recombinantly produced curli and provide evidence that they adopt a similar, well‐defined β‐solenoid arrangement. Curli subunits consist of five sequence repeats, resulting in severe spectral overlap. Using segmental isotope labeling, we obtained the unambiguous sequence‐specific resonance assignments and secondary structure of one repeat, and demonstrate that all repeats are most likely structurally equivalent. It’s a marvel of bacterial engineering: Amyloids are known for their structural polymorphisms, which hampers gaining a mechanistic understanding of their role in diseases. Bacteria produce the functional amyloid curli to form biofilms. Solid‐state NMR spectroscopy of biofilm‐derived and recombinant curli reveals a well‐defined, highly resilient conformation. Segmental isotope labeling allows a first indication of its structural features.