A molecular switch in RCK2 triggers sodium-dependent activation of K_Na1.1 (KCNT1) potassium channels.

ABSTRACT: The Na⁺-activated K⁺ channel K_Na1.1, encoded by the KCNT1 gene, is an important regulator of neuronal excitability. How intracellular Na⁺ ions bind and increase channel activity is not well understood. Analysis of K_Na1.1 channel structures indicate that there is a large twisting of the βN-αQ loop in the intracellular RCK2 domain between the inactive and Na⁺-activated conformations, with a lysine (K885, human subunit numbering) close enough to potentially form a salt bridge with an aspartate (D839) in βL in the Na⁺-activated state. Concurrently, an aspartate (D884) adjacent in the same loop adopts a position within a pocket formed by the βO strand. In carrying out mutagenesis and electrophysiology with human K

SUBMITTER: Cole BA 

PROVIDER: S-EPMC11309980 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature