Approaches to Forming a Water-soluble Extracellular Domain From α3 Subunits of Nicotinic Acetylcholine Receptors
MetadataShow full item record
Obtaining structural information on the extracellular domain (ECD) of α3 subunits of nicotinic acetylcholine receptors (nAChRs) by x-ray crystallography is desirable for the design of drugs intended to therapeutically target specific nAChRs and treat the various diseases and disorders caused by nAChR complications such as epilepsy, Alzheimer’s disease, Parkinson’s disease and other disorders of the nervous system. Separating the ECD from the rest of the structure is advantageous because the transmembrane domains make nAChRs difficult to crystallize. In order to explore the possibility of creating a water soluble ECD from the α3 subunits of nAChRs through the proteolysis of the ECD away from the transmembrane domains, the nAChR expression yield of mutant α3 nAChR subunits containing a flexible linker at the ECD/M1 interface was measured. The flexible linker used was an 18 amino acid sequence consisting of the residues alanine-glycine-serine repeated six times (6xAGS) and was designed as a possible flexible environment in which to contain a protease site. The nAChR yield, as measured by yield of [3H]epibatidine binding sites, was much lower for the α3 nAChR subunits containing the flexible linker at the ECD/M1 interface than for the control subunits without the linker. Therefore, the 6xAGS flexible linker is not the optimum environment in which to contain a protease site in α3 nAChR subunits.
Frankovich, Victoria Lea (2014). Approaches to Forming a Water-soluble Extracellular Domain From α3 Subunits of Nicotinic Acetylcholine Receptors. Honors and Undergraduate Research. Available electronically from