9KL0

Structure of hSGLT2-MAP17 complex in the substrate-free inward-facing conformation in the presence of potassium

Summary for 9KL0

• Entry DOI: 10.2210/pdb9kl0/pdb
• EMDB information: 62398
• Descriptor: Sodium/glucose cotransporter 2, PDZK1-interacting protein 1, mFab90-H, ... (4 entities in total)
• Functional Keywords: glucose transporter, sglt, sodium glucose transporter, membrane protein, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 104198.84

Authors

Chen, L.,Cui, W.,Sun, Z. (deposition date: 2024-11-14, release date: 2025-09-03)

Primary citation

Cui, W.,Sun, Z.,Xu, J.,Liu, X.,Kang, Y.,Chen, L.
Mechanism of substrate recognition and release of human SGLT2.
Nat Commun, 16:7140-7140, 2025

PubMed Abstract: 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 Å 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.

PubMed: 40759649
DOI: 10.1038/s41467-025-62421-6

Experimental method

ELECTRON MICROSCOPY (3.16 Å)