8YQ5

Cryo-EM structure of a de novo designed transmembrane protein tmZC8-BTB

Summary for 8YQ5

• Entry DOI: 10.2210/pdb8yq5/pdb
• Related: 8YQ6 9M05
• EMDB information: 39496 39497 63538
• Descriptor: de novo designed ion channel, DODECYL-BETA-D-MALTOSIDE (2 entities in total)
• Functional Keywords: de novo design, ion channels, de novo protein
• Biological source: synthetic construct
• Total number of polymer chains: 5
• Total formula weight: 134034.06

Authors

Lu, P.L.,Zhou, C. (deposition date: 2024-03-19, release date: 2025-09-24, Last modification date: 2026-01-07)

Primary citation

Zhou, C.,Li, H.,Wang, J.,Qian, C.,Xiong, H.,Chu, Z.,Shao, Q.,Li, X.,Sun, S.,Sun, K.,Zhu, A.,Wang, J.,Jin, X.,Yang, F.,Gamal El-Din, T.M.,Li, B.,Huang, J.,Wu, K.,Lu, P.
De novo designed voltage-gated anion channels suppress neuron firing.
Cell, 188:7495-, 2025

PubMed Abstract: Design of ion channels responsive to environmental cues has significant implications in modulating cellular activities and sensor development, but it remains a significant challenge due to the complexities involved in designing stimuli-induced conformational changes in proteins. Here, we report the accurate de novo design of voltage-gated anion channels, namely dVGACs. dVGACs adopt a 15-helix pentameric architecture featuring arginine constrictions within the transmembrane span and show voltage-dependent anions currents in patch-clamp experiments. Cryo-electron microscopy (cryo-EM) structures of dVGACs closely align with the design models. Cryo-EM structures and molecular dynamics simulations suggest that the arginine constrictions undergo voltage-induced conformational changes, serving as both a voltage sensor and a selectivity filter as designed. Notably, the anion selectivity and voltage sensitivity of dVGACs can be tuned through targeted mutations for suppressing neuronal firing in situ. The ability to create ion channels with custom-designed conformational changes refreshes our insights into membrane biophysics and unveils diverse potential applications.

PubMed: 41106381
DOI: 10.1016/j.cell.2025.09.023

Experimental method

ELECTRON MICROSCOPY (3.3 Å)