2.2 Å Cryo-EM Tetra-Protofilament Structure of the Hamster Prion 108-144 Fibril Reveals an Ordered Water Channel in the Center

Fibrils of the hamster prion peptide (sHaPrP, sequence 108-144) were prepared in an acidic solution, and their structure was solved by cryogenic electron microscopy with a resolution of 2.23 angstrom based on the gold-standard Fourier shell correlation (FSC) curve. The fibril has a novel architecture that has never been found in other amyloid fibrils. Each fibril is assembled by four protofilaments (PFs) and has an ordered water channel in the center. Each protofilament contains three beta-strands (125-130, 133-135, and 138-141) arranged in an R-shaped construct. The structural data indicate that these three beta-strand segments are the most amyloidogenic region of the prion peptide/protein and might be the site of nucleation during fibrillization under conditions without denaturants.

Automated summary

Fibrils of the hamster prion peptide have a unique structure with a water channel, and the three beta-strand segments are identified as the most amyloidogenic region that initiates fibrillization.