High-resolution characterization of ex vivo AAT polymers by solution-state NMR spectroscopy.

ABSTRACT: Serpins, protease inhibitors whose regulated conformational instability renders them susceptible to mutations that cause misfolding, represent a system for the study of non-amyloid protein aggregation. The E342K "Z" variant of α-1-antitrypsin (AAT) undergoes oligomeric self-assembly into polymer chains that are associated with liver and lung pathologies in AAT deficiency. Structural characterization of polymers from human tissue has been limited by their heterogeneity and flexibility; here, we have studied their internal structure, which provides insights into the molecular linkage and the pathway by which they are formed. NMR spectra of heat-induced ¹³C-ILV-methyl-labeled polymers, and ¹H-methyl spectra of liver-derived polymers, show equivalence to that of AAT in a

SUBMITTER: Lowen SM 

PROVIDER: S-EPMC12057664 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature