Download Bulk and annular lipid composition of nicotinic acetylcholine

“Bulk and annular lipid composition of nicotinic acetylcholine receptor in the Torpedo
californica electric organ”
The nicotinic acetylcholine receptor (nAChR) it’s a transmembrane protein that
has been used as a model for studying the processes regulated by lipid-protein
interactions. The alteration in the receptor structure or kinetic cause a decreasing
activity that has been implicated in a multiple pathologies including memory loss and
depression like Alzheimer’s disease, and other cognitive disorders. Because the X-ray
structure of AChR has not yet been solved since its hydrophobic character hampers its
successful crystallization, it’s important to understand the mechanism of the receptor in
order to develop new drug therapies. The nAChRs is in intimate contact with the annular
lipids in its native membrane and its stability and functionally depend on the lipid
environments.
In order to obtain a functional nAChR for future X-ray studies, a detergent that
mimic the native environment of the receptor it’s essential. Previously work in our lab
had determined the bulk lipid composition of the Torpedo californica (Tc) electric organ,
a rich source of muscle-type nAChR. Based on these results we choose a family of
lipid-like-detergents for the solubilization of the Tc electric organ. We will perform lipid
analysis on each of the detergent-solubilized nAChR preparations that yield functional
receptors using gas chromatography mass spectrometry (GC/MS) and high
performance liquid chromatography mass spectrometry (HPLC-MS) to determine the
cholesterol, phospholipid head group, and acyl composition in the detergent-solubilized
nAChR. These experiments will provide the information required for a comprehensive
lipid-based study based on correlations with the functional activity.