7yiy - Revision history

OCA at 09:30, 20 March 2024

OCA — Wed, 20 Mar 2024 09:30:29 GMT

←Older revision		Revision as of 09:30, 20 March 2024
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	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/SPTC2_HUMAN SPTC2_HUMAN] Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex displays a preference for C18-CoA substrate. Plays an important role in de novo sphyngolipid biosynthesis which is crucial for adipogenesis (By similarity).[UniProtKB:P97363]<ref>PMID:19416851</ref> <ref>PMID:19648650</ref> <ref>PMID:20920666</ref>		[https://www.uniprot.org/uniprot/SPTC2_HUMAN SPTC2_HUMAN] Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex displays a preference for C18-CoA substrate. Plays an important role in de novo sphyngolipid biosynthesis which is crucial for adipogenesis (By similarity).[UniProtKB:P97363]<ref>PMID:19416851</ref> <ref>PMID:19648650</ref> <ref>PMID:20920666</ref>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	The ORM/ORMDL family proteins function as regulatory subunits of the serine palmitoyltransferase (SPT) complex, which is the initiating and rate-limiting enzyme in sphingolipid biosynthesis. This complex is tightly regulated by cellular sphingolipid levels, but the sphingolipid sensing mechanism is unknown. Here we show that purified human SPT-ORMDL complexes are inhibited by the central sphingolipid metabolite ceramide. We have solved the cryo-EM structure of the SPT-ORMDL3 complex in a ceramide-bound state. Structure-guided mutational analyses reveal the essential function of this ceramide binding site for the suppression of SPT activity. Structural studies indicate that ceramide can induce and lock the N-terminus of ORMDL3 into an inhibitory conformation. Furthermore, we demonstrate that childhood amyotrophic lateral sclerosis (ALS) variants in the SPTLC1 subunit cause impaired ceramide sensing in the SPT-ORMDL3 mutants. Our work elucidates the molecular basis of ceramide sensing by the SPT-ORMDL complex for establishing sphingolipid homeostasis and indicates an important role of impaired ceramide sensing in disease development.

-	Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis.,Xie T, Liu P, Wu X, Dong F, Zhang Z, Yue J, Mahawar U, Farooq F, Vohra H, Fang Q, Liu W, Wattenberg BW, Gong X Nat Commun. 2023 Jun 13;14(1):3475. doi: 10.1038/s41467-023-39274-y. PMID:37308477<ref>PMID:37308477</ref>	+	==See Also==
-		+	*[[Serine palmitoyltransferase 3D structures\|Serine palmitoyltransferase 3D structures]]
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class~~=~~"pdbe-citations 7yiy" style~~=~~"background-color:#fffaf0;"></div>~~	+
	== References ==		== References ==
	<references/>		<references/>

OCA at 05:38, 5 July 2023

OCA — Wed, 05 Jul 2023 05:38:15 GMT

←Older revision		Revision as of 05:38, 5 July 2023
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-	'''Unreleased structure'''

-	The entry ~~7yiy~~ is ~~ON HOLD until 2024~~-07-18	+	==Cryo-EM structure of SPT-ORMDL3 complex==
		+	<StructureSection load='7yiy' size='340' side='right'caption='[[7yiy]], [[Resolution\|resolution]] 2.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[7yiy]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YIY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YIY FirstGlance]. <br>
		+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 2.7Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=Z1T:N-[(2S,3R,4E)-1,3-dihydroxyoctadec-4-en-2-yl]tetracosanamide'>Z1T</scene></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7yiy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yiy OCA], [https://pdbe.org/7yiy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yiy RCSB], [https://www.ebi.ac.uk/pdbsum/7yiy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yiy ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/SPTC2_HUMAN SPTC2_HUMAN] Hereditary sensory and autonomic neuropathy type 1. The disease is caused by variants affecting the gene represented in this entry. SPTLC2 disease mutations cause a shift in the substrate specificity of SPT resulting in the alternative use of L-alanine and L-glycine over its canonical substrate L-serine. This leads to the production of 1-deoxysphingolipids that cannot be correctly metabolized (PubMed:23658386).<ref>PMID:23658386</ref> <ref>PMID:26573920</ref>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/SPTC2_HUMAN SPTC2_HUMAN] Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 constitutes the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC2-SPTSSB complex displays a preference for C18-CoA substrate. Plays an important role in de novo sphyngolipid biosynthesis which is crucial for adipogenesis (By similarity).[UniProtKB:P97363]<ref>PMID:19416851</ref> <ref>PMID:19648650</ref> <ref>PMID:20920666</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The ORM/ORMDL family proteins function as regulatory subunits of the serine palmitoyltransferase (SPT) complex, which is the initiating and rate-limiting enzyme in sphingolipid biosynthesis. This complex is tightly regulated by cellular sphingolipid levels, but the sphingolipid sensing mechanism is unknown. Here we show that purified human SPT-ORMDL complexes are inhibited by the central sphingolipid metabolite ceramide. We have solved the cryo-EM structure of the SPT-ORMDL3 complex in a ceramide-bound state. Structure-guided mutational analyses reveal the essential function of this ceramide binding site for the suppression of SPT activity. Structural studies indicate that ceramide can induce and lock the N-terminus of ORMDL3 into an inhibitory conformation. Furthermore, we demonstrate that childhood amyotrophic lateral sclerosis (ALS) variants in the SPTLC1 subunit cause impaired ceramide sensing in the SPT-ORMDL3 mutants. Our work elucidates the molecular basis of ceramide sensing by the SPT-ORMDL complex for establishing sphingolipid homeostasis and indicates an important role of impaired ceramide sensing in disease development.

-	~~Authors~~:	+	Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis.,Xie T, Liu P, Wu X, Dong F, Zhang Z, Yue J, Mahawar U, Farooq F, Vohra H, Fang Q, Liu W, Wattenberg BW, Gong X Nat Commun. 2023 Jun 13;14(1):3475. doi: 10.1038/s41467-023-39274-y. PMID:37308477<ref>PMID:37308477</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 7yiy" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Gong X]]
		+	[[Category: Liu P]]
		+	[[Category: Xie T]]

OCA at 15:19, 7 September 2022

OCA — Wed, 07 Sep 2022 15:19:13 GMT

←Older revision		Revision as of 15:19, 7 September 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7yiy is ON HOLD	+	The entry 7yiy is ON HOLD until 2024-07-18

	Authors:		Authors:

OCA: Protected "7yiy" [edit=sysop:move=sysop]

OCA — Wed, 27 Jul 2022 16:27:04 GMT

Protected "7yiy" [edit=sysop:move=sysop]

←Older revision

Revision as of 16:27, 27 July 2022

OCA: New page: '''Unreleased structure''' The entry 7yiy is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 27 Jul 2022 16:27:03 GMT

New page: '''Unreleased structure''' The entry 7yiy is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7yiy is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]