Amyloid Forming Human Lysozyme Intermediates are Stabilized by Non-Native Amide-π Interactions.

ABSTRACT: Mutational variants of human lysozyme cause a rare but fatal hereditary systemic amyloidosis by populating an intermediate state that self-assembles into amyloid fibrils. However, this intermediate state is recalcitrant to detailed structural investigation, as it is only transiently and sparsely populated. Here, this work investigates the intermediate state of an amyloid-forming human lysozyme variant (I59T) using CEST and CPMG RD NMR at low pH. ¹⁵N CEST profiles probe the thermal unfolding of the native state into the denatured ensemble and reveal a distinct intermediate state. Global fitting of ¹⁵N CEST and CPMG data provides kinetic and thermodynamic parameters, characterizing the intermediate state populated at 0.6%. ¹H CEST data further confirm the pre

SUBMITTER: Ahn M 

PROVIDER: S-EPMC12442690 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature