The potassium channel KcsA and its interaction with the lipid bilayer

Abstract

The crystal structure of the K+ channel KcsA explains many features of ion channel function. The selectivity filter corresponds to a narrow region about 12 Along and 3 A wide, lined by carbonyl groups of the peptide backbone, through which a K+ ion can only move ina dehydrated form. The selectivity filter opens into a central, water-filled cavity leading to a gating site on the intracellular side of the channel. The channel is tetrameric, each monomer containing two transmembrane a helices, M1 and M2. Helix M1 faces the lipid bi-layer and helix M2 faces the central channel pore; the M2 helices participate in subunit-subunit interactions. Helices M1 and M2 in each subunit pack as a pair of antiparallel coils with a heptad repeat, but the M2 helices of neighbouring subunits show fewer interactions, crossing at an angle of about -40 degrees. Trp residues at the ends of the transmembrane a helices form clear girdles on the two faces of the membrane, which, together with girdles of charged residues, define a hydrophobic thickness of about 37 A for the channel. Binding constants for phosphatidylcholines to KcsA vary with fatty acyl chain length, the optimum chain length being C22. A phosphatidylcholine with this chain length gives a bilayer of thickness about 34 A in the liquid crystalline phase, matching the hydrophobic thickness of the protein. However, a typical biological membrane has a hydrophobic thickness of about 27 A. Thus either the transmembrane a helices of KcsA are more tilted in the native membrane than they are in the crystal structure, or the channel is under stress in the native membrane. The efficiency of hydrophobic matching between KcsA and the surrounding lipid bilayer is high over the chain length range C10-C24. The channel requires the presence of some anionic lipids for function, and fluorescence quenching studies show the presence of two classes of lipid binding site on KcsA; at one class of site (nonannular sites) anionic phospholipids bind more strongly than phosphatidylcholine, whereas at the other class of site (annular sites) phosphatidylcholines and anionic phospholipids bind with equal affinity.

Saturated and cis/trans Unsaturated Acyl CoA Esters Differentially Regulate Wild-Type and Polymorphic β-Cell ATP-Sensitive K+ Channels

“…Given the similarity in proposed crystal structure of the trans membrane domain of KcsA and KirBac1.1 and their sequence and structural homology with Kir6.2, we can speculate on potential interactions of acyl CoAs with Kir6.2 based on previous work performed on these related potassium channels (29). We have previously identified several positively charged residues in both the COOHterminal and NH 2 -terminal domains of the cytosolic portion of the Kir6.2 subunit that are important for acyl CoA binding.…”

Intrinsic Voltage Dependence of the Epithelial Na+ Channel Is Masked by a Conserved Transmembrane Domain Tryptophan

“…Here, they can act to anchor transmembrane domains, and through interactions with other residues form channel gates, depending on side chain orientation (16,19,(37)(38)(39)(40).…”

Membrane proteins: A new method enters the fold

“…1). Both hydrophobic mismatch and lateral packing pressure are known to have an impact on protein structure and the rate of protein folding (24)(25)(26), but the effect on protein stability is hard to quantify. Hong and Tamm (2) use their new technique to evaluate the contribution of bilayer characteristics to protein folding.…”