Human nACh e -- Asp 175

hAsp175Asn

This mutation reduces the ACh affinity for receptors in the resting closed state. Even though occupancy of the mutant site still promotes gating, the overall gating is impaired because of an effect independent of the ACh occupancy.

The site D175 is found to localize to the entrance of the ACh binding cavity when mapped on a structural model of the AChR binding site. At the same time, eN182Y localizes to the interface with the a subunit. This suggests that the protein chain with these two residues rearranges during receptor desensitization.

This mutation was found in a patient with myasthenic syndrome and was also studied with eN182Y.

Sine SM, Shen XM, Wang HL, Ohno K, Lee WY, Tsujino A, Brengmann J, Bren N, Vajsar J, Engel WG (2002) Naturally Occurring Mutations at the Acetylcholine Receptor Binding Site Independenlty Alter ACh Binding and Channel Gating. Journal of General Physiology 120(4):483-496

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