ArticleBiochemistry2014
A conformational investigation of propeptide binding to the integral membrane protein γ-glutamyl carboxylase using nanodisc hydrogen exchange mass spectrometry.
Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- GGCX-Associated Phenotypes: An Overview in Search of Genotype-Phenotype Correlations.International journal of molecular sciences · 2017Pooled it
- Structural and functional insights into γ-glutamyl carboxylase-factor IX interaction: implications for vitamin K-dependent bleeding disorders.Haematologica · 2026Article
- The Nanodisc System for Investigating Protein-Lipid Interactions.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Mass spectrometry footprinting reveals microsomal CYP2A6 structural changes induced by interaction with its reductase flavin mononucleotide domain.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase.Nature communications · 2025Article
- Article
- Article
- MSe Collision Energy Optimization for the Analysis of Membrane Proteins Using HDX-cIMS.Journal of the American Society for Mass Spectrometry · 2024Article
- Hydrogen/deuterium exchange-mass spectrometry of integral membrane proteins in native-like environments: current scenario and the way forward.Essays in biochemistry · 2023Article
- Advances in Hydrogen/Deuterium Exchange Mass Spectrometry and the Pursuit of Challenging Biological Systems.Chemical reviews · 2022Review
- Vitamin K - sources, physiological role, kinetics, deficiency, detection, therapeutic use, and toxicity.Nutrition reviews · 2022Review
- Vitamin K-Dependent γ-Glutamyl Carboxylase in Sertoli Cells Is Essential for Male Fertility in Mice.Molecular and cellular biology · 2021Article
- Article
- Nanodiscs and Mass Spectrometry: Making Membranes Fly.International journal of mass spectrometry · 2020Article
- A glimpse into the molecular mechanism of integral membrane proteins through hydrogen-deuterium exchange mass spectrometry.Protein science : a publication of the Protein Society · 2020Review
- Hydrogen-deuterium exchange mass spectrometry of membrane proteins in lipid nanodiscs.Chemistry and physics of lipids · 2019Review
- Tracking Higher Order Protein Structure by Hydrogen-Deuterium Exchange Mass Spectrometry.Protein and peptide letters · 2019Review
- Optimized Workflow for Selecting Peptides for HDX-MS Data Analyses.Journal of the American Society for Mass Spectrometry · 2018Article
- Topological Dissection of the Membrane Transport Protein Mhp1 Derived from Cysteine Accessibility and Mass Spectrometry.Analytical chemistry · 2017Article
- Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Gamma (γ)-glutamyl carboxylase (GGCX) is an integral membrane protein responsible for the post-translational catalytic conversion of select glutamic acid (Glu) residues to γ-carboxy glutamic acid (Gla) in vitamin K-dependent (VKD) proteins. Understanding the mechanism of carboxylation and the role of GGCX in the vitamin K cycle is of biological interest in the development of therapeutics for blood coagulation disorders. Historically, biophysical investigations and structural characterizations of GGCX have been limited due to complexities involving the availability of an appropriate model membrane system. In previous work, a hydrogen exchange mass spectrometry (HX MS) platform was developed to study the structural configuration of GGCX in a near-native nanodisc phospholipid environment. Here we have applied the nanodisc-HX MS approach to characterize specific domains of GGCX that exhibit structural rearrangements upon binding the high-affinity consensus propeptide (pCon; AVFLSREQANQVLQRRRR). pCon binding was shown to be specific for monomeric GGCX-nanodiscs and promoted enhanced structural stability to the nanodisc-integrated complex while maintaining catalytic activity in the presence of carboxylation co-substrates. Noteworthy modifications in HX of GGCX were prominently observed in GGCX peptides 491-507 and 395-401 upon pCon association, consistent with regions previously identified as sites for propeptide and glutamate binding. Several additional protein regions exhibited minor gains in solvent protection upon propeptide incorporation, providing evidence for a structural reorientation of the GGCX complex in association with VKD carboxylation. The results herein demonstrate that nanodisc-HX MS can be utilized to study molecular interactions of membrane-bound enzymes in the absence of a complete three-dimensional structure and to map dynamic rearrangements induced upon ligand binding.
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Registered trials
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