9kmn

From Proteopedia

(Difference between revisions)

Current revision

Structure of hSGLT2-MAP17 complex in the substrate-bound inward-facing conformation

Structural highlights

9kmn is a 4 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.47Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SC5A2_HUMAN Familial renal glucosuria. The disease is caused by variants affecting the gene represented in this entry.

Function

SC5A2_HUMAN Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:20980548, PubMed:28592437, PubMed:34880493). Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney (By similarity).[UniProtKB:Q923I7]^[1] ^[2] ^[3]

Publication Abstract from PubMed

Glucose is a vital energy source essential for life and human health. Sodium-glucose cotransporter 2 (SGLT2) is a sodium-glucose symporter that utilizes the electrochemical gradient of sodium to reabsorb glucose from kidney filtrate back into circulation. SGLT2 plays a crucial role in maintaining blood glucose homeostasis and is an important drug target for type 2 diabetes. Despite its significance, the mechanisms by which SGLT2 recognizes and releases substrates during its transport cycle remain largely unknown. Here, we present structures of human SGLT2 in complex with a glucose analogue in the occluded conformation at 2.6 A resolution, revealing a detailed hydrogen bonding network at the substrate binding site that governs substrate recognition. Additionally, structures of SGLT2 in both the substrate-bound inward-facing conformation and the substrate-free inward-facing conformations illustrate the structural changes that occur during substrate release into cytosol. Our structural analysis, combined with mutagenesis results, identifies specific polar interactions that are essential for maintaining the outer and inner gates in their closed conformations.

Mechanism of substrate recognition and release of human SGLT2.,Cui W, Sun Z, Xu J, Liu X, Kang Y, Chen L Nat Commun. 2025 Aug 4;16(1):7140. doi: 10.1038/s41467-025-62421-6. PMID:40759649^[4]

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

References

↑ Hummel CS, Lu C, Loo DD, Hirayama BA, Voss AA, Wright EM. Glucose transport by human renal Na+/D-glucose cotransporters SGLT1 and SGLT2. Am J Physiol Cell Physiol. 2011 Jan;300(1):C14-21. doi:, 10.1152/ajpcell.00388.2010. Epub 2010 Oct 27. PMID:20980548 doi:http://dx.doi.org/10.1152/ajpcell.00388.2010
↑ Coady MJ, Wallendorff B, Lapointe JY. Characterization of the transport activity of SGLT2/MAP17, the renal low-affinity Na(+)-glucose cotransporter. Am J Physiol Renal Physiol. 2017 Aug 1;313(2):F467-F474. PMID:28592437 doi:10.1152/ajprenal.00628.2016
↑ Niu Y, Liu R, Guan C, Zhang Y, Chen Z, Hoerer S, Nar H, Chen L. Structural basis of inhibition of the human SGLT2-MAP17 glucose transporter. Nature. 2022 Jan;601(7892):280-284. PMID:34880493 doi:10.1038/s41586-021-04212-9
↑ Cui W, Sun Z, Xu J, Liu X, Kang Y, Chen L. Mechanism of substrate recognition and release of human SGLT2. Nat Commun. 2025 Aug 4;16(1):7140. PMID:40759649 doi:10.1038/s41467-025-62421-6

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/9kmn"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9kmn is ON HOLD
+==Structure of hSGLT2-MAP17 complex in the substrate-bound inward-facing conformation==
+<StructureSection load='9kmn' size='340' side='right'caption='[[9kmn]], [[Resolution|resolution]] 2.47&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9kmn]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9KMN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9KMN 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]] 2.47&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EFW:(2~{S},3~{R},4~{R},5~{S},6~{R})-5-fluoranyl-6-(hydroxymethyl)oxane-2,3,4-triol'>A1EFW</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=9kmn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9kmn OCA], [https://pdbe.org/9kmn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9kmn RCSB], [https://www.ebi.ac.uk/pdbsum/9kmn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9kmn ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/SC5A2_HUMAN SC5A2_HUMAN] Familial renal glucosuria. The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/SC5A2_HUMAN SC5A2_HUMAN] Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:20980548, PubMed:28592437, PubMed:34880493). Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney (By similarity).[UniProtKB:Q923I7]<ref>PMID:20980548</ref> <ref>PMID:28592437</ref> <ref>PMID:34880493</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Glucose is a vital energy source essential for life and human health. Sodium-glucose cotransporter 2 (SGLT2) is a sodium-glucose symporter that utilizes the electrochemical gradient of sodium to reabsorb glucose from kidney filtrate back into circulation. SGLT2 plays a crucial role in maintaining blood glucose homeostasis and is an important drug target for type 2 diabetes. Despite its significance, the mechanisms by which SGLT2 recognizes and releases substrates during its transport cycle remain largely unknown. Here, we present structures of human SGLT2 in complex with a glucose analogue in the occluded conformation at 2.6 A resolution, revealing a detailed hydrogen bonding network at the substrate binding site that governs substrate recognition. Additionally, structures of SGLT2 in both the substrate-bound inward-facing conformation and the substrate-free inward-facing conformations illustrate the structural changes that occur during substrate release into cytosol. Our structural analysis, combined with mutagenesis results, identifies specific polar interactions that are essential for maintaining the outer and inner gates in their closed conformations.
-Authors:
+Mechanism of substrate recognition and release of human SGLT2.,Cui W, Sun Z, Xu J, Liu X, Kang Y, Chen L Nat Commun. 2025 Aug 4;16(1):7140. doi: 10.1038/s41467-025-62421-6. PMID:40759649<ref>PMID:40759649</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 9kmn" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Mus musculus]]
+[[Category: Chen L]]
+[[Category: Cui W]]
+[[Category: Sun Z]]

9kmn

From Proteopedia

Current revision

Structure of hSGLT2-MAP17 complex in the substrate-bound inward-facing conformation

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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