9DKF

Ca2+ bound aplysia Slo1 R202Q

Summary for 9DKF

• Entry DOI: 10.2210/pdb9dkf/pdb
• EMDB information: 46956
• Descriptor: BK channel, POTASSIUM ION, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: potassium channel, calcium-activated, voltage sensor, large conductance, membrane protein
• Biological source: Aplysia californica (California sea hare)
• Total number of polymer chains: 4
• Total formula weight: 479350.52

Authors

Gustavo, G.F.,Shen, R.,Latorre, R.,Perozo, E. (deposition date: 2024-09-08, release date: 2025-06-18, Last modification date: 2025-07-16)

Primary citation

Contreras, G.F.,Shen, R.,Latorre, R.,Perozo, E.
Structural basis of voltage-dependent gating in BK channels.
Nat Commun, 16:5846-5846, 2025

PubMed Abstract: The allosteric communication between the pore domain, voltage sensors, and Ca binding sites in the calcium- and voltage-activated K channel (BK) underlies its physiological role as the preeminent signal integrator in excitable systems. BK displays shallow voltage sensitivity with very fast gating charge kinetics, yet little is known about the molecular underpinnings of this distinctive behavior. Here, we explore the mechanistic basis of coupling between voltage-sensing domains (VSDs) and calcium sensors in Aplysia BK by locking the VSDs in their activated (R196Q and R199Q) and resting (R202Q) states, with or without calcium. Cryo-EM structures of these mutants reveal unique tilts at the S4 C-terminal end, together with large side-chain rotameric excursions of the gating charges. Notably, the VSD resting structure (R202Q) also revealed BK in its elusive, fully closed state, highlighting the reciprocal relation between calcium and voltage sensors. These structures provide a plausible path where voltage and Ca binding couple energetically and define the conformation of the pore domain and, thus, BK's full functional range.

PubMed: 40593533
DOI: 10.1038/s41467-025-60639-y

Experimental method

ELECTRON MICROSCOPY (2.6 Å)