Predicted condensation-related signatures localize to two C-terminal regions of the prion protein across cervid PRNP variants associated with chronic wasting disease

Variant-associated changes in cervid PRNP sequences localize to two C-terminal intervals—residues 126-140 and 220-230—without large shifts in overall intrinsic disorder.

• Why it matters: Genetic substitutions linked to chronic wasting disease susceptibility may alter PrPC condensation-relevant sequence properties, but where these effects concentrate along PrP has been unclear.
• What they did: The authors modeled 10 cervid PRNP variants on a shared mature PrP scaffold (residues 24-233) and computed intrinsic disorder, FuzDrop per-residue pDP and Sbind, pKa predictions, and discrete charge at pH 7.0, plus atomistic simulations of monomeric PrP.
• The result: FuzDrop predicted allele-dependent pDP changes at residues 126-140 and variant-specific Sbind changes at 220-230 (lower Sbind for S225F/Y and higher Sbind for elk-like Q226E), with simulations showing variant-sensitive backbone behavior and contacts, motivating direct tests.

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