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

TL;DR

This study revisits the polar clasp interactions in a bank vole PrP(168-176) prion protofibril structure, identifying new hydrogen bonds that differ from previously reported interactions, thereby enhancing understanding of prion fibril stabilization.

Contribution

The paper uncovers two novel intersheet hydrogen bonds in the prion protofibril, providing new insights into its structural stabilization mechanisms beyond prior crystallography reports.

Findings

Identified two new hydrogen bonds between strands A and B in the protofibril.

Revealed differences between experimental and revisited hydrogen bonding patterns.

Enhanced understanding of prion fibril stabilization mechanisms.

Abstract

On 2018-01-17 two electron crystallography structures (with PDB entries 6AXZ, 6BTK) on a prion protofibril of bank vole PrP(168-176) (a segment in the PrP $\beta$2-$\alpha$2 loop) were released into the PDB Bank. The paper published by [Nat Struct Mol Biol 25(2):131-134 (2018)] reports some polar clasps for these two crystal structures, and "an intersheet hydrogen bond between Tyr169 and the backbone carbonyl of Asn171 on an opposing strand." - this hydrogen bond is not between the neighbouring Chain B and Chain A directly. In addition, by revisiting the polar clasps, we found another two hydrogen bonds (B.Asn171@H-A.Gln172@OE1, B.Tyr169@OH-A.Gln172@N) between the strand A of one sheet and the opposing strand B of the mating sheet. For the neighbouring two single $\beta$-sheets AB, the two new hydrogen bonds are completely different from the experimental one (an intersheet hydrogen bond between Tyr169 and the backbone carbonyl of Asn171 on an opposing strand) in [Nat Struct Mol Biol 25(2):131-134 (2018)].