Title : Crystal structure of the extracellular
domain of
nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution
Abstract :
- We determined the crystal structure of the extracellular domain of the mouse nicotinic acetylcholine receptor ( nAChR ) alpha1 subunit bound to alpha-bungarotoxin at 1.94 A resolution
- This structure is the first atomic-resolution view of a nAChR subunit extracellular domain , revealing receptor-specific features such as the main immunogenic region ( MIR ), the signature Cys-loop and the N-linked carbohydrate chain
- The toxin binds to the receptor through extensive protein-protein and protein-sugar interactions
- To our surprise, the structure showed a well-ordered water molecule and two hydrophilic residues deep in the core of the alpha1 subunit
- The two hydrophilic core residues are highly conserved in nAChRs, but correspond to hydrophobic residues in the nonchannel homolog acetylcholine-binding proteins
- We carried out site-directed mutagenesis and electrophysiology analyses to assess the functional role of the glycosylation and the hydrophilic core residues
- Our structural and functional studies show essential features of the nAChR and provide new insights into the gating mechanism