Structural basis for nutrient-activated channel opening in bacterial spore germination receptors

Cofsky, J. C.; Ramirez-Guadiana, F. H.; Sobecks-Doherty, B. L.; Artzi, L.; Amon, J. D.; Gao, Y.; Dror, R.; del Marmol, J.; Rudner, D. Z.; Kruse, A. C.

doi:10.64898/2026.08.27.747515

bioRxiv · 10.64898/2026.08.27.747515

Structural basis for nutrient-activated channel opening in bacterial spore germination receptors

Cofsky, J. C.·Ramirez-Guadiana, F. H.·Sobecks-Doherty, B. L.·Artzi, L.·Amon, J. D.·Gao, Y.·Dror, R.·del Marmol, J.·Rudner, D. Z.·Kruse, A. C.

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Abstract

GerA-family germinant receptors were recently identified as ion channels that initiate germination of dormant bacterial spores in response to nutrients. Here we report 2.0-[A] cryo-electron microscopy structures of apo, agonist-bound, and antagonist-bound GerA, revealing a symmetric pentamer of heterotrimers. Signaling relies on two allosteric switches that radiate from the LeuT-type ligand-binding subunit in opposite directions, one away from the channel subunit and one directly toward it. A lipoprotein subunit reroutes the first switch and allosterically activates the second, promoting their convergence on the channel. Together, these rearrangements comprise a multipronged, cooperative signal transduction pathway that connects nutrient binding to pore opening in this new class of ligand-gated ion channels.

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Cofsky, J. C., Ramirez-Guadiana, F. H., Sobecks-Doherty, B. L., Artzi, L., Amon, J. D., Gao, Y., Dror, R., del Marmol, J., Rudner, D. Z., Kruse, A. C.. 2026-08-27. Structural basis for nutrient-activated channel opening in bacterial spore germination receptors. https://doi.org/10.64898/2026.08.27.747515

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