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GENETICS, CELL AND MOLECULAR BIOLOGY · CELL SIGNALLING

GATE 2020 BT, question 1: Cell signalling — solution and answer

GATE 2020 · BTQ.1 · 1 mark · MCQ Checked against the official key

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

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GATE 2020 BT question 1, as printedTap to open full size

Answer and worked solution

ANSWER

The answer is (B) aspartic acid.

Official key: B · Official answer key printed with the GATE 2020 BT paper (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, matching the official key.

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.

COMMON MISTAKE

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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