Nature 352, 64 - 67 (04 July 1991); doi:10.1038/352064a0

Extracellular domains mediating subunit interactions of muscle acetylcholine receptor

Xiao-Mei Yu & Zach W. Hall^*

Department of Physiology, School of Medicine, University of California at San Francisco, San Francisco, California 94143-0444, USA
^* To whom correspondence should be addressed.

LIGAND-gated ion channels, a major class of cell-surface proteins, have a pseudosymmetric structure with five highly homologous subunits arranged around a central ion pore¹. The correct assembly of each channel, whose subunit composition varies with cell type and stage of development, requires specific recognition between the subunits^2–4. Assembly of the pentameric form of the acetylcholine receptor from adult muscle (AChR; ₂) proceeds by a stepwise pathway starting with the formation of the hetero-dimers, e and . The heterodimers then associate with the subunit and with each other to form the complete receptor^5–7,21. We have now determined which parts of the subunits mediate the interactions during assembly of the adult form of the receptor from mouse muscle by using a chimaeric subunit in which the N-terminal and C-terminal extracellular domains are derived from the subunit with the remainder from the subunit. The e and subunits were chosen because the subunit forms a heterodimer with the a subunit in the pathway for assembly of the receptor,whereas the subunit does not. The chimaera can substitute for the but not the subunit in the oligomeric receptor, indicating that the a subunit specifically recognizes an extracellular domain of the e subunit.

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