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Donald Wu

@donaldwu.bsky.social

Chinese，gay，social liberal，high school student，have nothing with the CCP.

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PLOS Biology@plosbiology.org · last wk.

The human G6P transporter (SLC37A4) moves glucose-6-phosphate into the endoplasmic reticulum, supporting blood glucose stability and metabolism. This study solves the #structure of SLC37A4 in 3 conformations, providing insights substrate recognition & inhibition. 🧪#AcademicSky plos.io/4wo87tf

Conformational transitions and mechanistic model of substrate transport and inhibition. Top: Structural models of SLC37A4 in inward-open (left) and outward-open (right) conformations viewed in the membrane plane. The N-terminal domain (NTD) and C-terminal domain (CTD) are shown as yellow and cyan cartoons, respectively; horizontal black lines indicate the approximate membrane boundaries. The cluster of basic residues in the NTD (K29, R28 and K64) and K240 in the CTD are shown as green sticks. The putative translocation pathway is depicted as a transparent surface. In the inward-open state, G6P (red sticks) binds from the cytosolic side to the NTD basic cluster, while K240 in the CTD faces the cytosolic side. In the outward-open state, reorientation of the NTD and CTD exposes the binding site to the lumen, allowing G6P release and Pi binding, as indicated by arrows. Bottom: The schematic illustrates the conformational transitions between the inward-open, occluded, and outward-open states. The inhibition scenario (top) shows the binding of CHA to the inward-open state, which sterically hinders the transition to the occluded state (indicated by the red cross), thereby locking the transporter. In contrast, the functional antiport cycle (bottom) depicts the exchange of substrates: G6P binds to the inward-open state, facilitating the transition to the occluded state. Subsequently, the transporter shifts to the outward-open conformation to release G6P and accommodate the binding of inorganic phosphate (Pi) for transport in the reverse direction. Key residues (R28, K29, K64 on TM 1/2 and K240 on TM 7) involved in substrate/inhibitor recognition are highlighted.