Intracellular domain of nicotinic acetylcholine receptor: the importance of being unfolded

• Published in: Journal of neurochemistry Vol. 97; no. s1; pp. 63 - 67
• Main Authors: Kukhtina, V., Kottwitz, D., Strauss, H., Heise, B., Chebotareva, N., Tsetlin, V., Hucho, F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2006
• Subjects: Amino Acid Sequence; Animals; Basic Medicine; Binding Sites; Cell and Molecular Biology; Cell- och molekylärbiologi; eukaryotic linear motif; Gene Expression; intracellular domain; limited proteolysis; Magnetic Resonance Spectroscopy; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; nicotinic acetylcholine receptor; nuclear magnetic resonance; Peptide Hydrolases - metabolism; Protein Conformation; Protein Folding; Protein Subunits - chemistry; Receptors, Nicotinic - chemistry; Receptors, Nicotinic - genetics; Receptors, Nicotinic - physiology; secondary structure; Torpedo
• ISSN: 0022-3042; 1471-4159; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03468.x

Bioinformatics methods with subsequent verification by experimental data were applied to the structural investigation of the intracellular loop of the δ‐subunit of the nicotinic acetylcholine receptor (nAChR). Three complementary methods were used: prediction of secondary structure elements, prediction of ordered/disordered protein regions and prediction of short functional binding motifs. The output of five different algorithms was used for the secondary structure construction. Most of the intracellular domain is predicted to be unfolded. The predictions correlate well with the experimental data of limited proteolysis and NMR performed on the mostly monomeric fraction of heterologously expressed Torpedo intracellular domain protein. Twelve functional binding motifs within the disordered regions of the nAChR intracellular domain are predicted. Identification of proteins that interact with the intracellular domain will provide a better understanding of protein–protein interactions involved in nAChR assembly, trafficking and clustering.