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| Title | Cryo-EM structure of a phosphotransferase system glucose transporter stalled in an intermediate conformation. |
|---|---|
| Journal, issue, pages | J Struct Biol X, Vol. 11, Page 100124, Year 2025 |
| Publish date | Mar 5, 2025 |
 Authors | Patrick Roth / Dimitrios Fotiadis /  |
| PubMed Abstract | The phosphotransferase system glucose-specific transporter IICB serves as a central nutrient uptake system in bacteria. It transports glucose across the plasma membrane via the IIC domain and ...The phosphotransferase system glucose-specific transporter IICB serves as a central nutrient uptake system in bacteria. It transports glucose across the plasma membrane via the IIC domain and phosphorylates the substrate within the cell to produce the glycolytic intermediate, glucose-6-phosphate, through the IIB domain. Furthermore, IIC consists of a transport (TD) and a scaffold domain, with the latter being involved in dimer formation. Transport is mediated by an elevator-type mechanism within the IIC domain, where the substrate binds to the mobile TD. This domain undergoes a large-scale rigid-body movement relative to the static scaffold domain, translocating glucose across the membrane. Structures of elevator-type transporters are typically captured in either inward- or outward-facing conformations. Intermediate states remain elusive, awaiting structural determination and mechanistic interpretation. Here, we present a single-particle cryo-EM structure of purified, -dodecyl-β-D-maltopyranoside-solubilized IICB from . While the IIB protein domain is flexible remaining unresolved, the dimeric IIC transporter is found trapped in a hitherto unobserved intermediate conformational state. Specifically, the TD is located halfway between inward- and outward-facing states. Structural analysis revealed a specific -dodecyl-β-D-maltopyranoside molecule bound to the glucose binding site. The sliding of the TD is potentially impeded halfway due to the bulky nature of the ligand and a shift of the thin gate, thereby stalling the transporter. In conclusion, this study presents a novel conformational state of IIC, and provides new structural and mechanistic insights into a potential stalling mechanism, paving the way for the rational design of transport inhibitors targeting this critical bacterial metabolic process. |
 External links | J Struct Biol X / PubMed:40124667 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.53 Å |
| Structure data | EMDB-52311, PDB-9hnp: |
| Chemicals |  ChemComp-LMT: |
| Source |
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 Keywords | TRANSPORT PROTEIN / glucose transport protein / intermediate state / stalling / membrane protein |
escherichia coli (E. coli)