PXD052939 is an
original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Structural mechanism of γ-carboxylation coupled to vitamin K epoxidation at membrane interface |
| Description | Hemostasis and various non-hemostatic physiologies require γ-carboxylation of designated glutamates in vitamin K-dependent proteins (VKDPs), a process coupled with epoxidation of vitamin K hydroquinone (KH2) by membrane-integrated γ-carboxylase (VKGC). To understand this unique biochemistry, we determined cryo-electron microscopy structures of human VKGC in unbound form, with KH2 and four VKDPs possessing propeptides and glutamate-rich domains in different carboxylation states. VKGC recognizes propeptides via knob-and-hole interactions and adaptively binds tethered glutamate-containing segments. Propeptide binding allosterically triggers KH2 epoxidation, from which successive reactions generate a hydroxide superbase that deprotonates γ-carbon of a glutamate positioned by hydrogen bonding. A sealed hydrophobic tunnel protects and guides superbase diffusion to reach this carboxylation site across membrane interface. These structural insights and functional findings advance membrane enzymology and inspire anticoagulation therapies. |
| HostingRepository | PRIDE |
| AnnounceDate | 2025-12-22 |
| AnnouncementXML | Submission_2025-12-21_16:07:51.683.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Aaron Ammerman |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; |
| ModificationList | carboxylated residue; monohydroxylated residue; iodoacetic acid derivatized residue |
| Instrument | timsTOF Pro 2; Orbitrap Ascend |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|
| 0 | 2024-06-07 17:08:58 | ID requested | |
| ⏵ 1 | 2025-12-21 16:07:54 | announced | |
Publication List
Keyword List
| submitter keyword: Factor IX, vitamin K epoxide, VKGC, FIX,γ-carboxylation, TMG2 |
Contact List
| Weikai Li |
|---|
| contact affiliation | Department of Biochemistry Biophysics and Structural Biology, Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, St. Louis, Missouri, United States |
| contact email | weikai@wustl.edu |
| lab head | |
| Aaron Ammerman |
|---|
| contact affiliation | Washington University in St. Louis - Li Lab |
| contact email | a.ammerman@wustl.edu |
| dataset submitter | |
Full Dataset Link List
Dataset FTP location
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| PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD052939
- Label: PRIDE project
- Name: Structural mechanism of γ-carboxylation coupled to vitamin K epoxidation at membrane interface
