7yni › Citations

Structures of human SGLT in the occluded state reveal conformational changes during sugar transport.

<div class='caption-title'>Cryo-EM structure of human SGLT1-MAP17 complex.</div>
<div class='caption-title'>The closed intracellular gate and extracellular gate in the occluded state.</div>
<div class='caption-title'>Structural changes from the outward-open to the occluded conformation.</div>
Cui W, Niu Y, Sun Z, Liu R, Chen L
OpenAccess logo Nat Commun 14 2920 (2023)
Related entries: 7ynj, 7ynk

Cited: 2 times
EuropePMC logo PMID: 37217492

Abstract

Sodium-Glucose Cotransporters (SGLT) mediate the uphill uptake of extracellular sugars and play fundamental roles in sugar metabolism. Although their structures in inward-open and outward-open conformations are emerging from structural studies, the trajectory of how SGLTs transit from the outward-facing to the inward-facing conformation remains unknown. Here, we present the cryo-EM structures of human SGLT1 and SGLT2 in the substrate-bound state. Both structures show an occluded conformation, with not only the extracellular gate but also the intracellular gate tightly sealed. The sugar substrate are caged inside a cavity surrounded by TM1, TM2, TM3, TM6, TM7, and TM10. Further structural analysis reveals the conformational changes associated with the binding and release of substrates. These structures fill a gap in our understanding of the structural mechanisms of SGLT transporters.

Articles citing this publication (2)

  1. Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT. Khan F, Elgeti M, Grandfield S, Paz A, Naughton FB, Marcoline FV, Althoff T, Ermolova N, Wright EM, Hubbell WL, Grabe M, Abramson J. Nat Commun 14 7511 (2023)
  2. Transport and inhibition mechanism of the human SGLT2-MAP17 glucose transporter. Hiraizumi M, Akashi T, Murasaki K, Kishida H, Kumanomidou T, Torimoto N, Nureki O, Miyaguchi I. Nat Struct Mol Biol 31 159-169 (2024)


Quick links