Removal of phospho-head groups of membrane lipids immobilizes voltage sensors of K+ channels.
A fundamental question about the gating mechanism of voltage-activated K+ (Kv) channels is how five positively charged voltage-sensing residues in the fourth transmembrane segment are energetically stabilized, because they operate in a low-dielectric cell membrane. The simplest solution would be to pair them with negative charges. However, too few negatively charged channel residues are positioned for such a role. Recent studies suggest that some of the channel's positively charged residues are exposed to cell membrane phospholipids and interact with their head groups. A key question nevertheless remains: is the phospho-head of membrane lipids necessary for the proper function of the voltage sensor itself? Here we show that a given type of Kv channel may interact with several species of phospholipid and that enzymatic removal of their phospho-head creates an insuperable energy barrier for the positively charged voltage sensor to move through the initial gating step(s), thus immobilizing it, and also raises the energy barrier for the downstream step(s).
Xu
Yanping
Y
Department of Physiology, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, Pennsylvania 19104, USA.
Ramu
Yajamana
Y
Lu
Zhe
Z
D000818:Animals; D001419:Bacteria / Q000201:enzymology; D006868:Hydrolysis; D015640:Ion Channel Gating; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels / Q000378:metabolism; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014981:Xenopus
D008563:Membrane Lipids; D010710:Phosphates; D024642:Potassium Channels, Voltage-Gated; D011993:Recombinant Fusion Proteins; D051637:Shaker Superfamily of Potassium Channels; D013109:Sphingomyelins; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase; C105598:phosphatidylcholine-specific phospholipase C