Sub-ångström cryo-EM structure of a prion protofibril reveals a polar clasp

Abstract

The atomic structure of the infectious, protease-resistant, β-sheet-rich and fibrillar mammalian prion remains unknown. Through the cryo-EM method, MicroED, we reveal the sub-1Å resolution structure of a protofibril formed by a wild-type segment from the β2-α2 loop of the bank vole prion protein. The structure of this protofibril reveals a stabilizing network of hydrogen bonds that link polar zippers within a sheet, producing motifs we name ‘polar clasps’.

The polar clasps of a bank vole PrP(168–176) prion protofibril revisiting

“…This short paper revisited the 'polar clasps' and presented detailed HBs of the 'polar clasps'. We found out more HBs for the neighboring two β-strands, for the block of two β-sheets -each sheet being with two β-strands, and the most important, for the neighboring two single β-sheets AB, two new HBs B.Asn171@H-A.Gln172@OE1, B.Tyr169@OH-A.Gln172@N were found out, which is completely different from the experimental one (an intersheet HB between Tyr169 and the backbone carbonyl of Asn171 on an opposing strand) in [2].…”

“…Here we found 14 interchain HBs, including the 6 interchain HBs in Fig. 2 of [2] labeled by blue arrows. Table 3: The 20 HBs between the optimized AC Chains or within its each Chain for each pdb model: Fig.…”

“…The intrachain three HBs labeled by orange arrows in Fig. 2 of [2] are found here (see Tab. 4 and Fig.…”

“…The structures of some segments of PrP Sc have been determined, including the most recent bank vole PrP Sc (168-176) one of [2]. In Fig.…”

“…7, and the supplementary Tab. 2 of [2] where B is the C in here and C is the B here), including the Asn171@H-Gln172@OE1 in Tab. 4 linking B and A Chains, the HBs Asn171@O-Tyr169@H and Asn174@H-Asn173@OD1 linking A and D Chains, and Gln172@OE1-Asn171@H linking C and D Chains (Tab.…”