Asymmetry of the rat acetylcholine receptor subunits in the narrow region of the pore

A. Villarroel, S. Herlitze, V. Witzemann, M. Koenen, B. Sakmann

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Resumen

The acetylcholine receptor (AChR) channel is a pentameric protein in which every subunit contributes to the conducting parts of the pore. Recent studies of rat nicotinic AChR channels mutated in the α-subunit revealed that a threonine reside (αT264) in the transmembrane segment M2 forms part of the narrow region of the channel. We have mutated the residues at homologous positions in the β-, γ-, and δ-subunits and measured the resulting change in channel conductance. For all subunits the conductance is inversely related to the volume of the amino acid residue, suggesting that they form part of the channel narrow region. Exchanges of residues between subunits do not alter the conductance, suggesting a ring-like structure formed by homologous amino acids. To investigate the relative contribution of amino acid residue at these positions in determining the channel conductance, receptors carrying the same amino acid in each subunit in the narrow region were constructed. They form functional channels in which the conductance is inversely related to the volume of the amino acids in the narrow region. Channels in which the narrow region is formed by four scrines and one valine have the same conductance if the valine is located in the α-, β-, or γ-subunits, but it is smaller if the valine is located in the δ-subunit. The results suggest a structural asymmetry of the AChR channel in its narrow region formed by the hydroxylated amino acids of α-, γ- and δ-subunits, where the δ-subunit serine is a main determinant of the channel conductance.

Idioma originalEnglish
Páginas (desde-hasta)317-324
Número de páginas8
PublicaciónProceedings of the Royal Society B: Biological Sciences
Volumen249
N.º1326
DOI
EstadoPublished - 1992
Publicado de forma externa

ASJC Scopus Subject Areas

  • General Immunology and Microbiology
  • General Biochemistry,Genetics and Molecular Biology
  • General Environmental Science
  • General Agricultural and Biological Sciences

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