Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
G Protein-Coupled Inwardly-Rectifying Potassium Channels
-
Genes, Reporter
-
Glycine / metabolism
-
Heterotrimeric GTP-Binding Proteins / chemistry
-
Heterotrimeric GTP-Binding Proteins / metabolism*
-
Humans
-
Ion Channel Gating / physiology*
-
Models, Molecular
-
Molecular Sequence Data
-
Mutagenesis*
-
Oocytes / cytology
-
Oocytes / physiology
-
Potassium Channels / chemistry
-
Potassium Channels / genetics
-
Potassium Channels / metabolism*
-
Potassium Channels, Inwardly Rectifying*
-
Proline / metabolism
-
Protein Structure, Secondary
-
Protein Structure, Tertiary*
-
Protein Subunits / metabolism
-
Recombinant Fusion Proteins / genetics
-
Recombinant Fusion Proteins / metabolism
-
Sequence Alignment
-
Xenopus laevis
Substances
-
G Protein-Coupled Inwardly-Rectifying Potassium Channels
-
Potassium Channels
-
Potassium Channels, Inwardly Rectifying
-
Protein Subunits
-
Recombinant Fusion Proteins
-
Proline
-
Heterotrimeric GTP-Binding Proteins
-
Glycine
Associated data
-
GENBANK/U39195
-
PIR/A48206
-
PIR/S00479
-
PIR/S60172
-
PIR/S62694
-
SWISSPROT/Q16280