The (beta)gamma subunits of G proteins gate a K(+) channel by pivoted bending of a transmembrane segment.
The molecular mechanism of ion channel gating remains unclear. Using approaches such as proline scanning mutagenesis and homology modeling, we localize the gate of the K(+) channels controlled by the (beta)gamma subunits of G proteins at the pore-lining bundle crossing of the second transmembrane (TM2) helices. We show that the flexibility afforded by a highly conserved glycine residue in the middle of TM2 is crucial for channel gating. In contrast, flexibility introduced immediately below the gate disrupts gating. We propose that the force produced by channel-G(beta)gamma interactions is transduced through the rigid region below the helix bundle crossing to bend TM2 at the glycine that serves as a hinge and open the gate.
Jin
Taihao
T
Department of Physiology and Biophysics, Mount Sinai School of Medicine of New York University, New York, NY 10029, USA.
Peng
Luying
L
Mirshahi
Tooraj
T
Rohacs
Tibor
T
Chan
Kim W
KW
Sanchez
Roberto
R
Logothetis
Diomedes E
DE
D000595:Amino Acid Sequence; D000818:Animals; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D017930:Genes, Reporter; D005998:Glycine / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011392:Proline / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D014982:Xenopus laevis
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D011392:Proline; D020962:Heterotrimeric GTP-Binding Proteins; D005998:Glycine