The ligand binding domain of a ligand gated channel (LGC) has a serine residue, phosphorylation of which is essential for ligand binding. By site…
The ligand binding domain of a ligand gated channel (LGC) has a serine residue, phosphorylation of which is essential for ligand binding. By site directed mutagenesis it was replaced by aspartic acid. The likely consequences will be:
Select an option to attempt
Correct Answer: Option B
Explanation
Constitutively active ligand-binding domain using Asp mutation:The question describes engineering a constitutively active ligand-gated channel (LGC) by replacing Serine with Aspartate in the ligand-binding domain.Rational:• Serine is a neutral amino acid with a hydroxyl group (−OH) that can be phosphorylated (adding a negative charge −PO₃²⁻).• Aspartate has a carboxylate group (−COO⁻) — carries a permanent negative charge, mimicking constitutive phosphorylation.• If ligand binding (or the active state) involves a charge interaction at this Ser, replacing Ser→Asp creates a permanent negative charge that mimics the ligand-bound (active) state.• The LGC is then constitutively 'open' or active without needing ligand.This phosphomimetic substitution strategy is widely used in cell signalling research to create constitutively active proteins.Answer: Asp mimics phosphoserine (same negative charge), creating a constitutively active LGC.