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GATE 2020 BT Q.1: solution and answer

GATE 2020 · BTQ.1 · 1 mark · MCQ

Protein P becomes functional upon phosphorylation of a serine residue. Replacing this serine with ________ will result in a phosphomimic mutant of P.

  1. (A)

    alanine

  2. (B)

    aspartic acid

  3. (C)

    phenylalanine

  4. (D)

    lysine

See the question in the paper
GATE 2020 BT question 1Tap to open full size

Answer and solution

ANSWER

The answer is (B) aspartic acid.

Official answer: BSource: Official answer key, GATE 2020 BT (IIT Delhi)

  1. Phosphorylation of a serine adds a phosphate group to the side chain hydroxyl; at physiological pH this phosphate carries a net negative charge, which activates protein P.

  2. A phosphomimic mutation must reproduce this negative charge constitutively, independent of kinase activity, so the protein behaves as if permanently phosphorylated.

  3. Option A, alanine: small, nonpolar, uncharged, and lacks the hydroxyl needed for phosphorylation. This is the phospho null or phospho dead substitution, used to permanently block phosphorylation, the opposite of a phosphomimic. Not correct.

  4. Option B, aspartic acid: its carboxylate side chain is negatively charged at physiological pH, approximating the charge of a phosphoserine. Aspartate, along with glutamate, is the standard phosphomimetic substitution. Correct.

  5. Option C, phenylalanine: bulky, aromatic, hydrophobic, uncharged; cannot mimic a phosphate group's negative charge. Not correct.

  6. Option D, lysine: positively charged, electrostatically opposite to the phosphate group, so cannot act as a phosphomimic. Not correct.

  7. Hence replacing the serine with aspartic acid (B) creates the phosphomimic mutant.

KEY IDEA

A phosphomimetic substitution replaces the phosphorylatable residue (serine, threonine, or tyrosine) with a residue that is constitutively negatively charged, mimicking the negative charge added by the phosphate group without needing kinase activity.

WATCH OUT FOR

Confusing the phosphomimetic (aspartate or glutamate, mimics the always-on phosphorylated state) with the phospho-null/phospho-dead substitution (alanine, blocks phosphorylation and mimics the always-off unphosphorylated state); these are opposite tools and easy to swap under exam pressure.

From the GATE 2020 BT paper. Every question of this paper · Download the full paper · All 7 Cell signalling questions, with notes

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