Binding of anionic lipids to at least three non-annular sites on the potassium channel KcsA is required for channel opening

Marius, Phedra and Zagnoni, Michele and Sandison, Mairi E. and East, J. Malcolm and Morgan, Hywel and Lee, Anthony G. (2008) Binding of anionic lipids to at least three non-annular sites on the potassium channel KcsA is required for channel opening. Biophysical Journal, 94 (5). pp. 1689-1698. ISSN 0006-3495 (

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In addition to the annular or boundary lipids that surround the transmembrane surface of the potassium channel KcsA from Streptomyces lividans, x-ray crystallographic studies have detected one anionic lipid molecule bound at each protein-protein interface in the homotetrameric structure, at sites referred to as nonannular sites. The binding constant for phosphatidylglycerol at the nonannular sites has been determined using fluorescence quenching methods with a mutant of KcsA lacking the normal three lipid-exposed Trp residues. Binding is weak, with a binding constant of 0.42 +/- 0.06 in units of mol fraction, implying that the nonannular sites will only be approximately 70% occupied in bilayers of 100% phosphatidylglycerol. However, the nonannular sites show high selectivity for anionic lipids over zwitterionic lipids, and it is suggested that a change in packing at the protein-protein interface leads to a closing of the nonannular binding site in the unbound state. Increasing the anionic lipid content of the membrane leads to a large increase in open channel probability, from approximately 2.5% in the presence of 25 mol % phosphatidylglycerol to approximately 62% in 100 mol % phosphatidylglycerol. The relationship between open channel probability and phosphatidylglycerol content shows cooperativity. The data are consistent with a model in which three or four of the four nonannular sites in the KcsA homotetramer have to be occupied by anionic lipid for the channel to open. The conductance of the open channel increases with increasing concentration of anionic lipid, an effect possibly due to effects of anionic lipid on the concentration of K(+) close to the membrane surface.


Marius, Phedra, Zagnoni, Michele ORCID logoORCID:, Sandison, Mairi E. ORCID logoORCID:, East, J. Malcolm, Morgan, Hywel and Lee, Anthony G.;