8V3G
Cryo-EM structure of the KCa2.2 channel with inhibitor UCL 1684.
Summary for 8V3G
| Entry DOI | 10.2210/pdb8v3g/pdb |
| EMDB information | 42947 |
| Descriptor | Small conductance calcium-activated potassium channel protein 2, Calmodulin-1, POTASSIUM ION, ... (6 entities in total) |
| Functional Keywords | ion channel, transport protein-inhibitor complex, transport protein/inhibitor |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 8 |
| Total formula weight | 231515.04 |
| Authors | |
| Primary citation | Nam, Y.W.,Im, D.,Garcia, A.S.C.,Tringides, M.L.,Nguyen, H.M.,Liu, Y.,Orfali, R.,Ramanishka, A.,Pintilie, G.,Su, C.C.,Cui, M.,Logothetis, D.E.,Yu, E.W.,Wulff, H.,Chandy, K.G.,Zhang, M. Cryo-EM structures of the small-conductance Ca 2+ -activated K Ca 2.2 channel. Nat Commun, 16:3690-3690, 2025 Cited by PubMed Abstract: Small-conductance Ca-activated K (K2.1-K2.3) channels modulate neuronal and cardiac excitability. We report cryo-electron microscopy structures of the K2.2 channel in complex with calmodulin and Ca, alone or bound to two small molecule inhibitors, at 3.18, 3.50, 2.99 and 2.97 angstrom resolution, respectively. Extracellular S3-S4 loops in β-hairpin configuration form an outer canopy over the pore with an aromatic box at the canopy's center. Each S3-S4 β-hairpin is tethered to the selectivity filter in the neighboring subunit by inter-subunit hydrogen bonds. This hydrogen bond network flips the aromatic residue (Tyr362) in the filter's GYG signature by 180°, causing the outer selectivity filter to widen and water to enter the filter. Disruption of the tether by a mutation narrows the outer selectivity filter, realigns Tyr362 to the position seen in other K channels, and significantly increases unitary conductance. UCL1684, a mimetic of the bee venom peptide apamin, sits atop the canopy and occludes the opening in the aromatic box. AP14145, an analogue of a therapeutic for atrial fibrillation, binds in the central cavity below the selectivity filter and induces closure of the inner gate. These structures provide a basis for understanding the small unitary conductance and pharmacology of K2.x channels. PubMed: 40246884DOI: 10.1038/s41467-025-59061-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.1 Å) |
Structure validation
Download full validation report
