The nicotinic acetylcholine receptor (AChR) from the electric organ of Torpedo species is an oligomeric protein composed of α2βγδ subunits. Although much is known about its tertiary and quaternary structure, the conformation of the large extracellular domains of each of the subunits has not been analysed in detail. In order to obtain information about the spatial structure of the extracellular domain, we have expressed the N-terminal fragment 1209 of the Torpedo californica AChR α-subunitin in Escherichia coli Two vectors coding for a (His)6tag, either preceding or following the 1-209 sequence, were used and the recombinant proteins obtained (designated α1-209pET and α1-209pQE, respectively) were purified by affinity chromatography on a N12+-agarose column. The chemical structure of both proteins was verified by Edman degradation and mass spectrometry. The proteins were soluble in aqueous buffers but to make possible a comparison with the whole AChR or its isolated subunits, the recombinant proteins were analyzed both in aqueous solution and with the addition of detergents. The two proteins bound [125I]α-bungarotoxin with equal potency (K(D) ≃ 130 nM, B(max) ≃ 10 nmol·mg-1). Both were shown to interact with several monoclonal antibodies raised against purified Torpedo AChR. The circular dichroism (CD) spectra of the two proteins in aqueous solution revealed predominantly β-structure (50-56%), the fraction of αhelices amounting to 32-35%. Nonionic (β-octylglucoside) and zwitterionic (CHAPS) detergents did not appreciably change the CD spectra, while the addition of SDS or trifluoroethanol decreased the percentage of β-structure or increased the α-helicity, respectively. The predominance of β-structure is in accord with recent data on the N-terminal domain of the mouse muscle AChR α-subunit expressed in the mammalian cells [West et al. (1997) J. Biol Chem 272, 25 468]. Thus, expression in E. coli provides milligram amounts of the protein that retains several structural characteristics of the N-terminal domain of the Torpedo AChR α-subunit and appears to share with the latter a similar secondary structure. The expression of recombinant polypeptides representing functional domains of the AChR provides an essential first step towards a more detailed structural analysis.