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

Bioinformatics methods with subsequent verification by
experimental data were applied to the structural investigation
of the intracellular loop of the d-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.