INVESTIGADORES
BOUZAT Cecilia Beatriz
artículos
Título:
Structural Basis of the Different Gating Kinetics of Fetal and Adult Nicotinic
Autor/es:
BOUZAT, C.; BREN, N.; SINE, S.
Revista:
NEURON
Editorial:
CELL PRESS
Referencias:
Año: 1994 vol. 13 p. 1395 - 1402
ISSN:
0896-6273
Resumen:
Structure-function studies have identified key functional motifs in the acetylcholine receptor, including residues that contribute to the ion channel and to the ligand-binding sites. Little is known, however, about determinants of channel gating kinetics. To identify structural correlates of gating, we examined the structural basis of the fetal-to-adult decrease in channel open time conferred by the presence of the epsilon subunit in place of the gamma subunit. By constructing chimeras composed of segments of the epsilon and gamma subunits, we show that the main determinant of this kinetic change is a 30 residue segment of a predicted amphipathic helix located between transmembrane domains M3 and M4. Further subdividing the amphipathic helix revealed that either multiple residues or its overall conformation confers this regulation of channel kinetics. We also show that L440 and M442, conserved residues within M4 of the gamma subunit, contribute to long duration openings characteristic of the fetal receptor.