Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Molecular basis of vitamin-K-driven γ-carboxylation at the membrane interface.
Journal, issue, pages	Nature, Vol. 639, Issue 8055, Page 816-824, Year 2025
Publish date	Jan 29, 2025
Authors	Qing Cao / Aaron Ammerman / Mierxiati Saimi / Zongtao Lin / Guomin Shen / Huaping Chen / Jie Sun / Mengqi Chai / Shixuan Liu / Fong-Fu Hsu / Andrzej M Krezel / Michael L Gross / Jinbin Xu / Benjamin A Garcia / Bin Liu / Weikai Li /
PubMed Abstract	The γ-carboxylation of glutamate residues enables Ca-mediated membrane assembly of protein complexes that support broad physiological functions, including haemostasis, calcium homeostasis, immune ...The γ-carboxylation of glutamate residues enables Ca-mediated membrane assembly of protein complexes that support broad physiological functions, including haemostasis, calcium homeostasis, immune response and endocrine regulation. Modulating γ-carboxylation levels provides prevalent treatments for haemorrhagic and thromboembolic diseases. This unique post-translational modification requires vitamin K hydroquinone (KH) to drive highly demanding reactions 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 KH and four haemostatic and non-haemostatic proteins possessing propeptides and glutamate-rich domains in different carboxylation states. VKGC recognizes substrate proteins through knob-and-hole interactions with propeptides, thereby bringing tethered glutamate-containing segments for processive carboxylation within a large chamber that provides steric control. Propeptide binding also triggers a global conformational change to signal VKGC activation. Through sequential deprotonation and KH epoxidation, VKGC generates a free hydroxide ion as an exceptionally strong base that is required to deprotonate the γ-carbon of glutamate for CO addition. The diffusion of this superbase-protected and guided by a sealed hydrophobic tunnel-elegantly resolves the challenge of coupling KH epoxidation to γ-carboxylation across the membrane interface. These structural insights and extensive functional experiments advance membrane enzymology and propel the development of treatments for γ-carboxylation disorders.
External links	Nature / PubMed:39880037
Methods	EM (single particle)
Resolution	3.3 - 4.4 Å
Structure data	44935 9bvk EMDB-44935, PDB-9bvk: Vitamin K-dependent gamma-carboxylase with factor IX propeptide and glutamate-rich region and with vitamin K hydroquinone Method: EM (single particle) / Resolution: 3.6 Å 44936 9bvl EMDB-44936, PDB-9bvl: Vitamin K-dependent gamma-carboxylase with factor X propeptide and glutamate-rich region and with vitamin K hydroquinone Method: EM (single particle) / Resolution: 3.4 Å 44937 9bvm EMDB-44937, PDB-9bvm: Vitamin K-dependent gamma-carboxylase with protein C propeptide and glutamate-rich region and with vitamin K hydroquinone Method: EM (single particle) / Resolution: 3.4 Å 44939 9bvo EMDB-44939, PDB-9bvo: Vitamin K-dependent gamma-carboxylase in apo state Method: EM (single particle) / Resolution: 4.4 Å 44940 9bvp EMDB-44940, PDB-9bvp: Vitamin K-dependent gamma-carboxylase with TMG2 propeptide and glutamate-rich region and with vitamin K hydroquinone Method: EM (single particle) / Resolution: 3.3 Å 44941 9bvq EMDB-44941, PDB-9bvq: Vitamin K-dependent gamma-carboxylase with TMG2 propeptide and glutamate-rich region Method: EM (single particle) / Resolution: 3.3 Å 44942 9bvr EMDB-44942, PDB-9bvr: Vitamin K-dependent gamma-carboxylase with factor IX propeptide and partially carboxylated glutamate-rich region and with vitamin K hydroquinone and calcium Method: EM (single particle) / Resolution: 3.5 Å
Chemicals	PDB-1avc: BOVINE ANNEXIN VI (CALCIUM-BOUND) ChemComp-6PL: (4S,7R)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSAN-1-AMINIUM 4-OXIDE / phospholipidYM ChemComp-NAG*: 2-acetamido-2-deoxy-beta-D-glucopyranose
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / LYASE/SUBSTRATE / GGCX / VKGC / Vitamin K / VKCFD / Hemophilia B / Warfarin / Carboxylation / Blood Coagulaton / Calcium homeostasis / LYASE-SUBSTRATE complex / factor X / Protein C / LYASE / TMG / Gla