title: Potassium channel gating in the absence of the highly conserved glycine of the inner transmembrane helix.
abstract: Potassium channel activation regulates cellular excitability, such as in neuronal and cardiac cells. Regulation of ion channel activity relies on a switching mechanism between two major conformations, the open and closed states, known as gating. It has been suggested that potassium channels are generally gated via a pivoted mechanism the pore-lining helix (TM2) in the proximity of a glycine that is conserved in about 80% of potassium channels, even though about 20% of the channels lack a glycine at this position. Yet, as we show in G-protein gated potassium (Kir3) channels that lack a glycine at this position, the betagamma subunits of G-proteins can still stimulate channel activity. Our results suggest that the effect of mutation of the central glycine (at position 175 in Kir3.4) on betagamma-induced whole-cell currents is related to the extent of the interaction between residues located at the position of the central glycine and two residues, one located in the signature sequence of the selectivity filter (T149 in Kir3.4) and the other in the pore helix (E147 in Kir3.4). Our results also suggest that interactions with position 149 are more detrimental to channel function than interactions with position 147. The ability of Gbetagamma to overcome such restraining interactions is likely to depend on a combination of characteristics specific to each residue.
authors.affiliation: Department of Structural and Chemical Biology, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors.forename: Avia
authors.initials: A
authors.lastname: Rosenhouse-Dantsker
authors.forename: Diomedes E
authors.initials: DE
authors.lastname: Logothetis
mesh_terms: D000818:Animals; D001216:Asparagine; D001224:Aspartic Acid; D002462:Cell Membrane / Q000378:metabolism*; D003198:Computer Simulation; D017124:Conserved Sequence; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism; D018014:Gene Transfer Techniques; D018698:Glutamic Acid; D005973:Glutamine; D005998:Glycine; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics; D008239:Lysine; D008564:Membrane Potentials; D008958:Models, Molecular; D009154:Mutation; D009865:Oocytes; D011188:Potassium / Q000378:metabolism*; D011487:Protein Conformation; D021122:Protein Subunits; D012694:Serine; D013329:Structure-Activity Relationship; D013912:Threonine; D014981:Xenopus
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C118981:G-protein Beta gamma; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D021122:Protein Subunits; D005973:Glutamine; D013912:Threonine; D001224:Aspartic Acid; D018698:Glutamic Acid; D012694:Serine; D001216:Asparagine; D008239:Lysine; D011188:Potassium; D005998:Glycine