Section 3: Genetics, Cellular and Molecular Biology
Recombinant DNA technology
Subtopic: Fundamentals of Recombinant DNA technology
Question Statement:
The enzymes involved in ubiquitinylation of cell-cycle proteins are
Options:
(A) E1 and E2 only
(B) E1 and E3 only
(C) E1 and E4 only
(D) E1, E2 and E3
Official Answer Key:
D
Step-by-Step Solution & Explanation
### **Official Solution & Concept Analysis (GATE BT 2022 Q.43)**
**1. Governing Concept**:
- **Topic**: Molecular Cell Biology & Cell-Cycle Proteolysis
- Targeted polyubiquitination of cell-cycle regulators (e.g., cyclins, securin, CDK inhibitors like p27) requires the coordinated sequential action of three distinct classes of enzymes:
1. **E1 (Ubiquitin-activating enzyme)**: Forms a high-energy thioester bond with ubiquitin in an ATP-dependent step.
2. **E2 (Ubiquitin-conjugating enzyme)**: Trans-thiolates ubiquitin from E1 to an active-site cysteine on E2.
3. **E3 (Ubiquitin ligase)**: Specifically recognizes target cell-cycle substrates and transfers ubiquitin from E2 to a lysine $\epsilon$-amino group on the substrate (e.g., APC/C and SCF complexes).
- Thus, ubiquitination fundamentally requires **E1, E2, and E3**.
**2. Option Analysis**:
- **Option (A) is INCORRECT**: Lacks E3, which provides substrate specificity.
- **Option (B) is INCORRECT**: Lacks E2 conjugating intermediate.
- **Option (C) is INCORRECT**: E4 is a specialized polyubiquitin chain elongation factor, not the primary core triad.
- **Option (D) [E1, E2 and E3] is CORRECT**: The indispensable core three-enzyme cascade for substrate ubiquitination.
**3. Final Answer**:
- **Correct Choice**: **D**
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