9HNP
Cryo-EM structure of the glucose-specific PTS transporter IICB from E. coli in an intermediate state
Summary for 9HNP
| Entry DOI | 10.2210/pdb9hnp/pdb |
| EMDB information | 52311 |
| Descriptor | PTS system glucose-specific EIICB component, DODECYL-BETA-D-MALTOSIDE (2 entities in total) |
| Functional Keywords | glucose transport protein, intermediate state, stalling, membrane protein, transport protein |
| Biological source | Escherichia coli |
| Total number of polymer chains | 2 |
| Total formula weight | 105425.16 |
| Authors | |
| Primary citation | Roth, P.,Fotiadis, D. Cryo-EM structure of a phosphotransferase system glucose transporter stalled in an intermediate conformation. J Struct Biol X, 11:100124-100124, 2025 Cited by 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 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. PubMed: 40124667DOI: 10.1016/j.yjsbx.2025.100124 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.53 Å) |
Structure validation
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