8jf0

From Proteopedia

(Difference between revisions)

Current revision

Human sodium-dependent vitamin C transporter 1 in an intermediate state

Structural highlights

8jf0 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.5Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

S23A1_HUMAN Sodium:ascorbate cotransporter. Mediates electrogenic uptake of vitamin C, with a stoichiometry of 2 Na(+) for each ascorbate (PubMed:10556483, PubMed:10556521, PubMed:10631088, PubMed:36749388). Has retained some ancestral activity toward nucleobases such as urate, an oxidized purine. Low-affinity high-capacity sodium:urate cotransporter, may regulate serum urate levels by serving as a renal urate re-absorber (PubMed:36749388).^[1] ^[2] ^[3] ^[4] Inactive transporter.^[5]

Publication Abstract from PubMed

Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot synthesize vitamin C de novo from glucose, its uptake from dietary sources is essential, and is mediated by the sodium-dependent vitamin C transporter 1 (SVCT1). Despite its physiological significance in maintaining vitamin C homeostasis, the structural basis of the substrate transport mechanism remained unclear. Here, we report the cryo-EM structures of human SVCT1 in different states at 2.5-3.5 A resolutions. The binding manner of vitamin C together with two sodium ions reveals the counter ion-dependent substrate recognition mechanism. Furthermore, comparisons of the inward-open and occluded structures support a transport mechanism combining elevator and distinct rotational motions. Our results demonstrate the molecular mechanism of vitamin C transport with its underlying conformational cycle, potentially leading to future industrial and medical applications.

Dimeric transport mechanism of human vitamin C transporter SVCT1.,Kobayashi TA, Shimada H, Sano FK, Itoh Y, Enoki S, Okada Y, Kusakizako T, Nureki O Nat Commun. 2024 Jul 2;15(1):5569. doi: 10.1038/s41467-024-49899-2. PMID:38956111^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wang H, Dutta B, Huang W, Devoe LD, Leibach FH, Ganapathy V, Prasad PD. Human Na(+)-dependent vitamin C transporter 1 (hSVCT1): primary structure, functional characteristics and evidence for a non-functional splice variant. Biochim Biophys Acta. 1999 Nov 9;1461(1):1-9. PMID:10556483 doi:10.1016/s0005-2736(99)00182-0
↑ Daruwala R, Song J, Koh WS, Rumsey SC, Levine M. Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2. FEBS Lett. 1999 Nov 5;460(3):480-4. PMID:10556521 doi:10.1016/s0014-5793(99)01393-9
↑ Wang Y, Mackenzie B, Tsukaguchi H, Weremowicz S, Morton CC, Hediger MA. Human vitamin C (L-ascorbic acid) transporter SVCT1. Biochem Biophys Res Commun. 2000 Jan 19;267(2):488-94. PMID:10631088 doi:10.1006/bbrc.1999.1929
↑ Toyoda Y, Miyata H, Uchida N, Morimoto K, Shigesawa R, Kassai H, Nakao K, Tomioka NH, Matsuo H, Ichida K, Hosoyamada M, Aiba A, Suzuki H, Takada T. Vitamin C transporter SVCT1 serves a physiological role as a urate importer: functional analyses and in vivo investigations. Pflugers Arch. 2023 Apr;475(4):489-504. PMID:36749388 doi:10.1007/s00424-023-02792-1
↑ Wang H, Dutta B, Huang W, Devoe LD, Leibach FH, Ganapathy V, Prasad PD. Human Na(+)-dependent vitamin C transporter 1 (hSVCT1): primary structure, functional characteristics and evidence for a non-functional splice variant. Biochim Biophys Acta. 1999 Nov 9;1461(1):1-9. PMID:10556483 doi:10.1016/s0005-2736(99)00182-0
↑ Kobayashi TA, Shimada H, Sano FK, Itoh Y, Enoki S, Okada Y, Kusakizako T, Nureki O. Dimeric transport mechanism of human vitamin C transporter SVCT1. Nat Commun. 2024 Jul 2;15(1):5569. PMID:38956111 doi:10.1038/s41467-024-49899-2

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8jf0"

Categories: Homo sapiens | Large Structures | Kobayashi TA | Kusakizako T | Nureki O

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8jf0 is ON HOLD  until Paper Publication
+==Human sodium-dependent vitamin C transporter 1 in an intermediate state==
+<StructureSection load='8jf0' size='340' side='right'caption='[[8jf0]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8jf0]] is a 1 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=8JF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JF0 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]] 3.5&#8491;</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=8jf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jf0 OCA], [https://pdbe.org/8jf0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jf0 RCSB], [https://www.ebi.ac.uk/pdbsum/8jf0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jf0 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/S23A1_HUMAN S23A1_HUMAN] Sodium:ascorbate cotransporter. Mediates electrogenic uptake of vitamin C, with a stoichiometry of 2 Na(+) for each ascorbate (PubMed:10556483, PubMed:10556521, PubMed:10631088, PubMed:36749388). Has retained some ancestral activity toward nucleobases such as urate, an oxidized purine. Low-affinity high-capacity sodium:urate cotransporter, may regulate serum urate levels by serving as a renal urate re-absorber (PubMed:36749388).<ref>PMID:10556483</ref> <ref>PMID:10556521</ref> <ref>PMID:10631088</ref> <ref>PMID:36749388</ref>   Inactive transporter.<ref>PMID:10556483</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Vitamin C plays important roles as a cofactor in many enzymatic reactions and as an antioxidant against oxidative stress. As some mammals including humans cannot synthesize vitamin C de novo from glucose, its uptake from dietary sources is essential, and is mediated by the sodium-dependent vitamin C transporter 1 (SVCT1). Despite its physiological significance in maintaining vitamin C homeostasis, the structural basis of the substrate transport mechanism remained unclear. Here, we report the cryo-EM structures of human SVCT1 in different states at 2.5-3.5 A resolutions. The binding manner of vitamin C together with two sodium ions reveals the counter ion-dependent substrate recognition mechanism. Furthermore, comparisons of the inward-open and occluded structures support a transport mechanism combining elevator and distinct rotational motions. Our results demonstrate the molecular mechanism of vitamin C transport with its underlying conformational cycle, potentially leading to future industrial and medical applications.
-Authors:
+Dimeric transport mechanism of human vitamin C transporter SVCT1.,Kobayashi TA, Shimada H, Sano FK, Itoh Y, Enoki S, Okada Y, Kusakizako T, Nureki O Nat Commun. 2024 Jul 2;15(1):5569. doi: 10.1038/s41467-024-49899-2. PMID:38956111<ref>PMID:38956111</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8jf0" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Kobayashi TA]]
+[[Category: Kusakizako T]]
+[[Category: Nureki O]]

8jf0

From Proteopedia

Current revision

Human sodium-dependent vitamin C transporter 1 in an intermediate state

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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