9O85
Cryo-EM structure of KCa2.2_I/calmodulin channel in complex with rimtuzalcap
This is a non-PDB format compatible entry.
Summary for 9O85
| Entry DOI | 10.2210/pdb9o85/pdb |
| EMDB information | 70217 |
| Descriptor | Small conductance calcium-activated potassium channel protein 2, Calmodulin-1, POTASSIUM ION, ... (6 entities in total) |
| Functional Keywords | ion channel, small-conductance calcium-activated potassium channel, membrane protein, transport protein |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 8 |
| Total formula weight | 240460.25 |
| Authors | |
| Primary citation | Zhang, M.,Nam, Y.W.,Ramanishka, A.,Xu, Y.,Yasuda, R.M.,Im, D.,Cui, M.,Chandy, G.,Wulff, H. Structural basis for the subtype-selectivity of K Ca 2.2 channel activators. Res Sq, 2025 Cited by PubMed Abstract: Small-conductance (K2.2) and intermediate-conductance (K3.1) Ca-activated K channels are gated by a Ca-calmodulin dependent mechanism. NS309 potentiates the activity of both K2.2 and K3.1, while rimtuzalcap selectively activates K2.2. Rimtuzalcap has been used in clinical trials for the treatment of spinocerebellar ataxia and essential tremor. We report cryo-electron microscopy structures of K2.2 channels bound with NS309 and rimtuzalcap, in addition to K3.1 channels with NS309. The different conformations of calmodulin and the cytoplasmic HC helices in the two channels underlie the subtype-selectivity of rimtuzalcap for K2.2. Calmodulin's N-lobes in the K2.2 structure are far apart and undergo conformational changes to accommodate either NS309 or rimtuzalcap. Calmodulin's Nlobes in the K3.1 structure are closer to each other and are constrained by the HC helices of K3.1, which allows binding of NS309 but not of the bulkier rimtuzalcap. These structures provide a framework for structure-based drug design targeting K2.2 channels. PubMed: 40470184DOI: 10.21203/rs.3.rs-6568445/v1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.13 Å) |
Structure validation
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