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Mechanism of sphingolipid homeostasis revealed by structural analysis of Arabidopsis SPT-ORM1 complex
The serine palmitoyltransferase (SPT) complex catalyzes the first and rate-limiting step in sphingolipid biosynthesis in all eukaryotes. ORM/ORMDL proteins are negative regulators of SPT that respond to cellular sphingolipid levels. However, the molecular basis underlying ORM/ORMDL-dependent homeost...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Association for the Advancement of Science
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058238/ https://www.ncbi.nlm.nih.gov/pubmed/36989369 http://dx.doi.org/10.1126/sciadv.adg0728 |
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author | Liu, Peng Xie, Tian Wu, Xinyue Han, Gongshe Gupta, Sita D. Zhang, Zike Yue, Jian Dong, Feitong Gable, Kenneth Niranjanakumari, Somashekarappa Li, Wanyuan Wang, Lin Liu, Wenchen Yao, Ruifeng Cahoon, Edgar B. Dunn, Teresa M. Gong, Xin |
author_facet | Liu, Peng Xie, Tian Wu, Xinyue Han, Gongshe Gupta, Sita D. Zhang, Zike Yue, Jian Dong, Feitong Gable, Kenneth Niranjanakumari, Somashekarappa Li, Wanyuan Wang, Lin Liu, Wenchen Yao, Ruifeng Cahoon, Edgar B. Dunn, Teresa M. Gong, Xin |
author_sort | Liu, Peng |
collection | PubMed |
description | The serine palmitoyltransferase (SPT) complex catalyzes the first and rate-limiting step in sphingolipid biosynthesis in all eukaryotes. ORM/ORMDL proteins are negative regulators of SPT that respond to cellular sphingolipid levels. However, the molecular basis underlying ORM/ORMDL-dependent homeostatic regulation of SPT is not well understood. We determined the cryo–electron microscopy structure of Arabidopsis SPT-ORM1 complex, composed of LCB1, LCB2a, SPTssa, and ORM1, in an inhibited state. A ceramide molecule is sandwiched between ORM1 and LCB2a in the cytosolic membrane leaflet. Ceramide binding is critical for the ORM1-dependent SPT repression, and dihydroceramides and phytoceramides differentially affect this repression. A hybrid β sheet, formed by the amino termini of ORM1 and LCB2a and induced by ceramide binding, stabilizes the amino terminus of ORM1 in an inhibitory conformation. Our findings provide mechanistic insights into sphingolipid homeostatic regulation via the binding of ceramide to the SPT-ORM/ORMDL complex that may have implications for plant-specific processes such as the hypersensitive response for microbial pathogen resistance. |
format | Online Article Text |
id | pubmed-10058238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-100582382023-03-30 Mechanism of sphingolipid homeostasis revealed by structural analysis of Arabidopsis SPT-ORM1 complex Liu, Peng Xie, Tian Wu, Xinyue Han, Gongshe Gupta, Sita D. Zhang, Zike Yue, Jian Dong, Feitong Gable, Kenneth Niranjanakumari, Somashekarappa Li, Wanyuan Wang, Lin Liu, Wenchen Yao, Ruifeng Cahoon, Edgar B. Dunn, Teresa M. Gong, Xin Sci Adv Biomedicine and Life Sciences The serine palmitoyltransferase (SPT) complex catalyzes the first and rate-limiting step in sphingolipid biosynthesis in all eukaryotes. ORM/ORMDL proteins are negative regulators of SPT that respond to cellular sphingolipid levels. However, the molecular basis underlying ORM/ORMDL-dependent homeostatic regulation of SPT is not well understood. We determined the cryo–electron microscopy structure of Arabidopsis SPT-ORM1 complex, composed of LCB1, LCB2a, SPTssa, and ORM1, in an inhibited state. A ceramide molecule is sandwiched between ORM1 and LCB2a in the cytosolic membrane leaflet. Ceramide binding is critical for the ORM1-dependent SPT repression, and dihydroceramides and phytoceramides differentially affect this repression. A hybrid β sheet, formed by the amino termini of ORM1 and LCB2a and induced by ceramide binding, stabilizes the amino terminus of ORM1 in an inhibitory conformation. Our findings provide mechanistic insights into sphingolipid homeostatic regulation via the binding of ceramide to the SPT-ORM/ORMDL complex that may have implications for plant-specific processes such as the hypersensitive response for microbial pathogen resistance. American Association for the Advancement of Science 2023-03-29 /pmc/articles/PMC10058238/ /pubmed/36989369 http://dx.doi.org/10.1126/sciadv.adg0728 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Liu, Peng Xie, Tian Wu, Xinyue Han, Gongshe Gupta, Sita D. Zhang, Zike Yue, Jian Dong, Feitong Gable, Kenneth Niranjanakumari, Somashekarappa Li, Wanyuan Wang, Lin Liu, Wenchen Yao, Ruifeng Cahoon, Edgar B. Dunn, Teresa M. Gong, Xin Mechanism of sphingolipid homeostasis revealed by structural analysis of Arabidopsis SPT-ORM1 complex |
title | Mechanism of sphingolipid homeostasis revealed by structural analysis of Arabidopsis SPT-ORM1 complex |
title_full | Mechanism of sphingolipid homeostasis revealed by structural analysis of Arabidopsis SPT-ORM1 complex |
title_fullStr | Mechanism of sphingolipid homeostasis revealed by structural analysis of Arabidopsis SPT-ORM1 complex |
title_full_unstemmed | Mechanism of sphingolipid homeostasis revealed by structural analysis of Arabidopsis SPT-ORM1 complex |
title_short | Mechanism of sphingolipid homeostasis revealed by structural analysis of Arabidopsis SPT-ORM1 complex |
title_sort | mechanism of sphingolipid homeostasis revealed by structural analysis of arabidopsis spt-orm1 complex |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10058238/ https://www.ncbi.nlm.nih.gov/pubmed/36989369 http://dx.doi.org/10.1126/sciadv.adg0728 |
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