117. 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:
A. LGC becomes non-functional
B. LGC becomes constitutively active
C. No change in function
D. It will rapidly shift between active and inactive forms

Detailed Explanation:

Ligand Gated Channels (LGCs) are a class of ion channels that open in response to the binding of a specific chemical messenger (ligand). These channels often undergo regulation through phosphorylation, typically at serine, threonine, or tyrosine residues. Phosphorylation adds a negative charge, which induces conformational changes, enabling or enhancing ligand binding.

Given Context:

• A serine residue in the ligand-binding domain is phosphorylated for activity.

• Site-directed mutagenesis replaces this serine with aspartic acid.

Why This Matters:

Aspartic acid naturally carries a negative charge at physiological pH, mimicking the effect of phosphorylation. This is a common experimental strategy used to simulate a “phosphorylated” state of a protein without actual kinase activity.

Likely Consequences:

Since aspartic acid mimics phosphorylation, it can cause the receptor to behave as if it is always phosphorylated, even without actual modification. This can lead to ligand-independent activity or constitutive activation.

Correct Answer:

B. LGC becomes constitutively active

This type of mutation is widely studied in molecular biology to understand post-translational modifications and their roles in protein function, especially in signaling pathways.