Structural and mechanistic analysis of Ca²⁺-dependent regulation of transglutaminase 2 activity using a Ca²⁺-bound intermediate state.

ABSTRACT: Mammalian transglutaminases, a family of Ca²⁺-dependent proteins, are implicated in a variety of diseases. For example, celiac disease (CeD) is an autoimmune disorder whose pathogenesis requires transglutaminase 2 (TG2) to deamidate select glutamine residues in diet-derived gluten peptides. Deamidation involves the formation of transient γ-glutamyl thioester intermediates. Recent studies have revealed that in addition to the deamidated gluten peptides themselves, their corresponding thioester intermediates are also pathogenically relevant. A mechanistic understanding of this relevance is hindered by the absence of any structure of Ca²⁺-bound TG2. We report the X-ray crystallographic structure of human TG2 bound to an inhibitory gluten peptidomimetic and two Ca^2+<

SUBMITTER: Sewa AS 

PROVIDER: S-EPMC11252922 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature