Acetylcholine receptor assembly: subunit folding and oligomerization occur sequentially.

Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510.

The temperature sensitivity of nicotinic acetylcholine receptors (AChRs) from T. californica was used to identify steps in AChR subunit folding and oligomerization. Assembly intermediates were isolated by lowering to an assembly-permissive temperature. The earliest identifiable assembly intermediates, alpha beta gamma trimers, form minutes after subunit synthesis. alpha beta gamma delta tetramers are formed slowly by the addition of delta subunits to trimers, and finally a second alpha subunit is added to form alpha 2 beta gamma delta pentamers. Between these oligomerization steps, subunits fold as monitored by alpha-bungarotoxin-binding site formation, appearance of antigenic epitopes, changes in apparent molecular weight, and changes in detergent solubility. Subunit folding requires specific combinations of subunits and correlates in time with subunit additions, suggesting that these subunit folding events contribute to subunit recognition site formation during assembly.

PMID: 8334706 [PubMed - indexed for MEDLINE]