Diphtheria toxin mechanism involves ADP-ribosylation of Elongation Factor-2 (EF-2), halting protein synthesis. Which fragment of the toxin is responsible for ADP-ribosyltransferase activity, and what is the unique amino acid target?
- A Fragment B — targets a lysine residue on the 60S ribosomal protein
- B Fragment A — targets diphthamide (a modified histidine residue on EF-2) ✓
- C Fragment A — targets a methylated arginine residue on elongation factor 1
- D Fragment B — cleaves the peptide bond between EF-2 and GTP
Explanation
Diphtheria toxin is a single polypeptide with two functional domains: Fragment B (binding/translocation domain) mediates receptor binding (HB-EGF receptor) and pore formation for membrane translocation, while Fragment A contains the enzymatic ADP-ribosyltransferase activity. Fragment A catalyzes ADP-ribosylation of a unique post-translationally modified histidine residue called diphthamide (2-[3-carboxyamido-3-(trimethylammonio)propyl]-L-histidine) at position 715 of EF-2. This modification irreversibly inactivates EF-2, blocking translocation during translation. Pseudomonas exotoxin A has the same mechanism, also targeting diphthamide on EF-2.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.