Human nACh a -- Val 285

Species Original Mutated to Mutation
Human Val 285

Ile

Ala

Leu

V285I

V285A

V285L

Rat Equivalent Val 260    
Mouse Equivalent Val 260    

hVal285Ile

This mutation disrupts gating of the channel, slowing the rate of opening and speeding the rate of closing. There appeared to be decreased apparent affinity for ACh.

This mutation has been correlated with myasthenic syndrome.

Wang HL, Milone M, Ohno K, Shen XM, Tsujino A, Batocchi AP, Tonali P, Brengman J, Engel AG, Sine SM (1999) Acetylcholine Receptor M3 Domain: Stereochemical and Volume Contributions to Channel Gating Nature Neuroscience 2(3):226- 233

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hVal285Ala

The channel gating was strongly enhanced with this mutation to a smaller alanine. The rate of the channel opening increased, and the rate of the channel closing decreased.

Wang HL, Milone M, Ohno K, Shen XM, Tsujino A, Batocchi AP, Tonali P, Brengman J, Engel AG, Sine SM (1999) Acetylcholine Receptor M3 Domain: Stereochemical and Volume Contributions to Channel Gating Nature Neuroscience 2(3):226- 233

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hVal285Leu

This mutation showed even more impaired gating kinetics, suggesting that volume and stereochemistry of residue a285 affect channel gating.

Wang HL, Milone M, Ohno K, Shen XM, Tsujino A, Batocchi AP, Tonali P, Brengman J, Engel AG, Sine SM (1999) Acetylcholine Receptor M3 Domain: Stereochemical and Volume Contributions to Channel Gating Nature Neuroscience 2(3):226- 233

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