Maping the lipid protein interface of the Torpedo and muscle-type acetylcholine receptors (AChRs).  

 

The objective of this project is to complete the Try-Scan data for all the M3 and M4 lipid-exposed domains of the muscle-type AChRs to develop structural models that will be compared with the Torpedo AChR and with the most recent AChR structure (Unwin 2005). The structural models generated from Tryp-Scan data will be used to estimate: (1) spatial orientation of the helix relative to the interior of the protein, (2) overall secondary structure, (3) membrane crossing angle predictions, (4) altered patterns of hydrogen bonds inside the helix, (5) periodicity of the helix at the center and at the edge with the membrane, (6) potential deviations from helical structure, (7) prediction on the degree of lipid contact and (8) overall movement on each of the lipid exposed domains upon agonist activation. These parameters will be estimated for the closed and open states of the Torpedo and muscle-type AChRs. These structural models will be use to generate a detailed structural model of the AChR lipid interface for Torpedo and muscle-type AChRs. These studies will provide fundamental information to: (1) define the structure and spatial orientation of the lipid-exposed domains, (2) gain insight into the molecular basis for the lipid interaction and regulation of AChR function, (3) define the mechanistic link between lipid-exposed domains and the gating machinery of the AChR, (4) understand the structural basis for differential sensitivities of different nAChRs species to the lipid environment.