Referenced in: none

Automatically associated channels: BKβ , Slo1

Title: Charge substitution for a deep-pore residue reveals structural dynamics during BK channel gating.

Authors: Xixi Chen, Richard W Aldrich

Journal, date & volume: J. Gen. Physiol., 2011 Aug , 138, 137-54

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21746846

Abstract
The pore-lining amino acids of ion channel proteins reside on the interface between a polar (the pore) and a nonpolar environment (the rest of the protein). The structural dynamics of this region, which physically controls ionic flow, are essential components of channel gating. Using large-conductance, Ca(2+)-dependent K(+) (BK) channels, we devised a systematic charge-substitution method to probe conformational changes in the pore region during channel gating. We identified a deep-pore residue (314 in hSlo1) as a marker of structural dynamics. We manipulated the charge states of this residue by substituting amino acids with different valence and pKa, and by adjusting intracellular pH. We found that the charged states of the 314 residues stabilized an open state of the BK channel. With models based on known structures of related channels, we postulate a dynamic rearrangement of the deep-pore region during BK channel opening/closing, which involves a change of the degree of pore exposure for 314.