Channelpedia

PubMed 12941953


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Kir1.1 , Kir6.2



Title: Sur domains that associate with and gate KATP pores define a novel gatekeeper.

Authors: Andrey P Babenko, Joseph Bryan

Journal, date & volume: J. Biol. Chem., 2003 Oct 24 , 278, 41577-80

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12941953


Abstract
Structure-function analyses of K+ channels identify a common pore architecture whose gating depends on diverse signal sensing elements. The "gatekeepers" of the long, ATP-inhibited KIR6.0 pores of KATP channels are ABC proteins, SURs, receptors for channel opening and closing drugs. Several competing models for SUR/KIR coupling exist. We show that SUR TMD0, the N-terminal bundle of five transmembrane helices, specifically associates with KIR6.2, forcing nearly silent pores to burst like native KATP channels and enhancing surface expression. Inclusion of adjacent submembrane residues of L0, the linker between TMD0 and the stimulatory nucleotide- and drug-binding ABC core, generates constitutively active channels, whereas additional cytoplasmic residues counterbalance this activation establishing a relationship between the mean open and burst times of intact pores. SUR fragments, lacking TMD0, fail to modulate KIR. TMD0 is thus the domain that anchors SUR to the KIR pore. Consistent with data on chimeric ABCC/KIRs and a modeled channel structure, we propose that interactions of TMD0-L0 with the outer helix and N terminus of KIR bidirectionally modulate gating. The results explain and predict pathologies associated with alteration of the 5' ends of clustered ABCC8 (9)/KCNJ11 (8) genes.