Computational design and molecular dynamics simulations suggest the mode of substrate binding in ceramide synthases
© 2023. The Author(s)..
Until now, membrane-protein stabilization has relied on iterations of mutations and screening. We now validate a one-step algorithm, mPROSS, for stabilizing membrane proteins directly from an AlphaFold2 model structure. Applied to the lipid-generating enzyme, ceramide synthase, 37 designed mutations lead to a more stable form of human CerS2. Together with molecular dynamics simulations, we propose a pathway by which substrates might be delivered to the ceramide synthases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Nature communications - 14(2023), 1 vom: 22. Apr., Seite 2330 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zelnik, Iris D [VerfasserIn] |
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| Links: |
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| Themen: |
Ceramides |
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| Anmerkungen: |
Date Completed 25.04.2023 Date Revised 02.05.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-38047-x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM355912244 |
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| 245 | 1 | 0 | |a Computational design and molecular dynamics simulations suggest the mode of substrate binding in ceramide synthases |
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| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Until now, membrane-protein stabilization has relied on iterations of mutations and screening. We now validate a one-step algorithm, mPROSS, for stabilizing membrane proteins directly from an AlphaFold2 model structure. Applied to the lipid-generating enzyme, ceramide synthase, 37 designed mutations lead to a more stable form of human CerS2. Together with molecular dynamics simulations, we propose a pathway by which substrates might be delivered to the ceramide synthases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Ceramides |2 NLM | |
| 650 | 7 | |a dihydroceramide desaturase |2 NLM | |
| 650 | 7 | |a EC 1.3.1.- |2 NLM | |
| 650 | 7 | |a Oxidoreductases |2 NLM | |
| 650 | 7 | |a EC 1.- |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 700 | 1 | |a Mestre, Beatriz |e verfasserin |4 aut | |
| 700 | 1 | |a Weinstein, Jonathan J |e verfasserin |4 aut | |
| 700 | 1 | |a Dingjan, Tamir |e verfasserin |4 aut | |
| 700 | 1 | |a Izrailov, Stav |e verfasserin |4 aut | |
| 700 | 1 | |a Ben-Dor, Shifra |e verfasserin |4 aut | |
| 700 | 1 | |a Fleishman, Sarel J |e verfasserin |4 aut | |
| 700 | 1 | |a Futerman, Anthony H |e verfasserin |4 aut | |
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