Evidence map›Paper›PMID 28336574›Full record

ArticleJournal of lipid research2017

Switching head group selectivity in mammalian sphingolipid biosynthesis by active-site-engineering of sphingomyelin synthases.

Matthijs Kol, Radhakrishnan Panatala, Mirjana Nordmann, Leoni Swart, Leonie van Suijlekom, Birol Cabukusta, Angelika Hilderink, Tanja Grabietz, John G M Mina, Pentti Somerharju and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 36 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Toxoplasma ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  8. Article
  9. The foundations and development of lipidomics.Journal of lipid research · 2022
    Review
  10. Article
  11. Article
  12. Defective cortex glia plasma membrane structure underlies light-induced epilepsy inProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  13. Review
  14. Article
  15. Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 4 countries.

Matthijs KolMolecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, 49076 Osnabrück, Germany matthijs.kol@biologie.uni-osnabrueck.de holthuis@uos.de.
Radhakrishnan PanatalaMolecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, 49076 Osnabrück, Germany.
Mirjana NordmannMolecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, 49076 Osnabrück, Germany.
Leoni SwartMembrane Biochemistry and Biophysics, Bijvoet Center and Institute of Biomembranes, Utrecht University, 3584 CH Utrecht, The Netherlands.
Leonie van SuijlekomMembrane Biochemistry and Biophysics, Bijvoet Center and Institute of Biomembranes, Utrecht University, 3584 CH Utrecht, The Netherlands.
Birol CabukustaMolecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, 49076 Osnabrück, Germany.
Angelika HilderinkMolecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, 49076 Osnabrück, Germany.
Tanja GrabietzMolecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, 49076 Osnabrück, Germany.
John G M MinaMolecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, 49076 Osnabrück, Germany.
Pentti SomerharjuMedical Biochemistry, Institute of Biomedicine, University of Helsinki, Helsinki 00014, Finland.
Sergei KorneevMolecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, 49076 Osnabrück, Germany.
Fikadu G TafesseMolecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239.
Joost C M HolthuisMolecular Cell Biology Division, Department of Biology/Chemistry, University of Osnabrück, 49076 Osnabrück, Germany matthijs.kol@biologie.uni-osnabrueck.de holthuis@uos.de.
Osnabrück University · DEUtrecht University · NLOregon Health & Science University · USUniversity of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

SM is a fundamental component of mammalian cell membranes that contributes to mechanical stability, signaling, and sorting. Its production involves the transfer of phosphocholine from phosphatidylcholine onto ceramide, a reaction catalyzed by SM synthase (SMS)1 in the Golgi and SMS2 at the plasma membrane. Mammalian cells also synthesize trace amounts of the SM analog, ceramide phosphoethanolamine (CPE), but the physiological relevance of CPE production is unclear. Previous work revealed that SMS2 is a bifunctional enzyme producing both SM and CPE, whereas a closely related enzyme, SMS-related protein (SMSr)/SAMD8, acts as a monofunctional CPE synthase in the endoplasmic reticulum. Using domain swapping and site-directed mutagenesis on enzymes expressed in defined lipid environments, we here identified structural determinants that mediate the head group selectivity of SMS family members. Notably, a single residue adjacent to the catalytic histidine in the third exoplasmic loop profoundly influenced enzyme specificity, with Glu permitting SMS-catalyzed CPE production and Asp confining the enzyme to produce SM. An exchange of exoplasmic residues with SMSr proved sufficient to convert SMS1 into a bulk CPE synthase. This allowed us to establish mammalian cells that produce CPE rather than SM as the principal phosphosphingolipid and provide a model of the molecular interactions that impart catalytic specificity among SMS enzymes.

Indexed as

Catalytic DomainMutagenesis, Site-DirectedAmino Acid SequenceCell Line, TumorHumansProtein DomainsSphingolipidsSubstrate SpecificityTransferases (Other Substituted Phosphate Groups)phosphatidylcholine-ceramide phosphocholine transferaseSphingolipidsTransferases (Other Substituted Phosphate Groups)cell-free expressionceramide phosphoethanolamineclick chemistryenzyme mechanismsGolgi apparatuslipid biochemistrylipidomicsmodel membranesprotein engineering

Identifiers

PMID28336574
PMCPMC5408615
OpenAlexW2355630172

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.