Molecular basis of vitamin-K-driven γ-carboxylation at the membrane interface.

ABSTRACT: The γ-carboxylation of glutamate residues enables Ca²⁺-mediated membrane assembly of protein complexes that support broad physiological functions, including haemostasis, calcium homeostasis, immune response and endocrine regulation^1-4. Modulating γ-carboxylation levels provides prevalent treatments for haemorrhagic and thromboembolic diseases⁵. This unique post-translational modification requires vitamin K hydroquinone (KH₂) to drive highly demanding reactions⁶ catalysed by the membrane-integrated γ-carboxylase (VKGC). Here, to decipher the underlying mechanisms, we determined cryo-electron microscopy structures of human VKGC in unbound form, with KH₂ and four haemostatic and non-haemostatic proteins possessing propeptides a

SUBMITTER: Cao Q 

PROVIDER: S-EPMC12701776 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature