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GYGD pore motifs in neighbouring potassium channel subunits interact to determine ion selectivity
Author(s) -
Chapman Mark L.,
Krovetz Howard S.,
VanDongen Antonius M. J.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.0021m.x
Subject(s) - kcsa potassium channel , gating , potassium channel , ion channel , chemistry , conductance , selectivity , biophysics , protein subunit , membrane potential , ligand gated ion channel , stereochemistry , crystallography , biochemistry , biology , receptor , gene , physics , condensed matter physics , catalysis
1 Cells maintain a negative resting membrane potential through the constitutive activity of background K + channels. A novel multigene family of such K + channels has recently been identified. A unique characteristic of these K + channels is the presence of two homologous, subunit‐like domains, each containing a pore‐forming region. Sequence co‐variations in the GYGD signature motifs of the two pore regions suggested an interaction between neighbouring pore domains. 2 Mutations of the GYGD motif in the rat drk1 (Kv2.1) K + channel showed that the tyrosine (Y) position was important for K + selectivity and single channel conductance, whereas the aspartate (D) position was a critical determinant of open state stability. 3 Tandem constructs engineered to mimic the GYGx‐GxGD pattern seen in two‐domain K + channels delineated a co‐operative intersubunit interaction between the Y and D positions, which determined ion selectivity, conductance and gating. 4 In the bacterial KcsA K + channel crystal structure, the equivalent aspartate residue (D80) does not directly interact with permeating K + ions. However, the data presented here show that the D position is able to fine‐tune ion selectivity through a functional interaction with the Y position in the neighbouring subunit. 5 These data indicate a physiological basis for the extensive sequence variation seen in the GYGD motifs of two‐domain K + channels. It is suggested that a cell can precisely regulate its resting membrane potential by selectively expressing a complement of two‐domain K + channels.