ArticleThe Journal of biological chemistry2014
Structural basis for autoinhibition of CTP:phosphocholine cytidylyltransferase (CCT), the regulatory enzyme in phosphatidylcholine synthesis, by its membrane-binding amphipathic helix.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Preclinical efficacy of a gene therapy forMolecular therapy. Advances · 2026Article
- Biosynthesis of Phosphatidylethanolamine and Phosphatidylcholine via the Kennedy Pathway in Cancer and Other Pathological Conditions.International journal of molecular sciences · 2026Review
- AlphaFlex: Ensembles of the human proteome representing disordered regions.bioRxiv : the preprint server for biology · 2025Article
- Functions of Arabidopsis CTP:phosphocholine cytidylyltransferase 1 in phosphatidylcholine biosynthesis and root growth.Plant physiology · 2025Article
- Article
- The CYTOLD and ERTOLD pathways for lipid droplet-protein targeting.Trends in biochemical sciences · 2022Review
- Stressed Lipid Droplets: How Neutral Lipids Relieve Surface Tension and Membrane Expansion Drives Protein Association.The journal of physical chemistry. B · 2021Article
- Identification of a nuclear localization signal in the Plasmodium falciparum CTP: phosphocholine cytidylyltransferase enzyme.Scientific reports · 2020Article
- Leveraging a gain-of-function allele of Caenorhabditis elegans paqr-1 to elucidate membrane homeostasis by PAQR proteins.PLoS genetics · 2020Article
- Differential dephosphorylation of CTP:phosphocholine cytidylyltransferase upon translocation to nuclear membranes and lipid droplets.Molecular biology of the cell · 2020Article
- Lipid synthesis and transport are coupled to regulate membrane lipid dynamics in the endoplasmic reticulum.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
- Article
- Interdomain communication in the phosphatidylcholine regulatory enzyme, CCTα, relies on a modular αE helix.The Journal of biological chemistry · 2019Article
- Remodeling of the interdomain allosteric linker upon membrane binding of CCTα pulls its active site close to the membrane surface.The Journal of biological chemistry · 2019Article
- Disease-linked mutations in the phosphatidylcholine regulatory enzyme CCTα impair enzymatic activity and fold stability.The Journal of biological chemistry · 2019Article
- Phosphatidylcholine synthesis regulates triglyceride storage and chylomicron secretion by Caco2 cells.Journal of lipid research · 2018Article
- Structural determinants of the catalytic mechanism of Plasmodium CCT, a key enzyme of malaria lipid biosynthesis.Scientific reports · 2018Article
- An auto-inhibitory helix in CTP:phosphocholine cytidylyltransferase hijacks the catalytic residue and constrains a pliable, domain-bridging helix pair.The Journal of biological chemistry · 2018Article
- How CCTα puts a leash on phospholipid synthesis.The Journal of biological chemistry · 2018Article
- Diacylglycerol Acyltransferase 1 Is Regulated by Its N-Terminal Domain in Response to Allosteric Effectors.Plant physiology · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
ctpphosphocholine cytidylyltransferase (CCT) interconverts between an inactive soluble and active membrane-bound form in response to changes in membrane lipid composition. Activation involves disruption of an inhibitory interaction between the αE helices at the base of the active site and an autoinhibitory (AI) segment in the regulatory M domain and membrane insertion of the M domain as an amphipathic helix. We show that in the CCT soluble form the AI segment functions to suppress kcat and elevate the Km for CTP. The crystal structure of a CCT dimer composed of the catalytic and AI segments reveals an AI-αE interaction as a cluster of four amphipathic helices (two αE and two AI helices) at the base of the active sites. This interaction corroborates mutagenesis implicating multiple hydrophobic residues within the AI segment that contribute to its silencing function. The AI-αE interaction directs the turn at the C-terminal end of the AI helix into backbone-to-backbone contact with a loop (L2) at the opening to the active site, which houses the key catalytic residue, lysine 122. Molecular dynamics simulations suggest that lysine 122 side-chain orientations are constrained by contacts with the AI helix-turn, which could obstruct its engagement with substrates. This work deciphers how the CCT regulatory amphipathic helix functions as a silencing device.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.