Nature of the 5' residue in the M2 domain affects function of the human alpha 1 beta 1 GABAA receptor.
The effects on the functional properties of the alpha 1 beta 1 GABAA receptor when the 5' (alpha 1 Val260; beta 1 Ile255) hydrophobic amino acids in the second transmembrane (M2) region were changed to threonine were examined. In response to a saturating concentration of GABA, the current evoked in mutant receptors showed a decreased rate of desensitization and at equilibrium was a greater fraction of the peak current than in wild-type receptors. The half-saturation concentration of the peak current response to GABA in mutant receptors was comparable to that in wild-type receptors, but the Hill coefficient was reduced to less than one. It was concluded that the 5' amino acids in the M2 region have a role in the conformational changes that occur within the alpha 1 beta 1 GABAA receptor in response to GABA.
Birnir
B
B
Membrane Biology Program, John Curtin School of Medical Research, Australian National University, Canberra, Australia. bryndia.birnir@anu.edu.au
Tierney
M L
ML
Lim
M
M
Cox
G B
GB
Gage
P W
PW
D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D008566:Membranes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017354:Point Mutation / Q000502:physiology*; D011487:Protein Conformation; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism*; D018411:Spodoptera; D013912:Threonine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D011963:Receptors, GABA-A; D013912:Threonine; D005680:gamma-Aminobutyric Acid