Recombinant Mycobacterium leprae ATP synthase subunit c (atpE) is a bioengineered protein derived from the atpE gene, which encodes a critical component of the F₀ sector of the F₁F₀-ATP synthase. This enzyme is essential for ATP synthesis and proton translocation in M. leprae, a pathogen causing leprosy. The recombinant form is produced heterologously in systems like E. coli, yeast, or baculovirus, often with N-terminal His-tags for purification and structural studies .
C-Ring Assembly: Subunit c oligomerizes into a ring (typically 9 subunits in mycobacteria), creating a proton channel .
Proton Translocation: Residues Glu61 and Tyr64 coordinate proton movement, while Asp28 and Ile66 stabilize the proton-binding cleft .
Drug Targeting: Mutations in subunit c (e.g., Asp28→Gly, Glu61→Asp) confer resistance to TMC207, a drug targeting the mycobacterial C-ring .
Recombinant atpE is produced for structural, biochemical, and vaccine-related research.
| Condition | ATP Synthase Activity | Biological Impact |
|---|---|---|
| Wild-type | Low ATP hydrolysis | Prevents ATP waste, maintains proton motive force |
| Δα533–545 (deletion) | High ATP hydrolysis | Disrupts ATP/ADP homeostasis, lethal if unchecked |
While not directly interacting with subunit c, M. leprae HSP18 binds ATP, enhancing its chaperone function. This interaction may indirectly stabilize ATP synthase under stress .
| Feature | M. leprae atpE | M. tuberculosis atpE |
|---|---|---|
| Subunit c Stoichiometry | c₉ | c₉ or c₁₀ |
| Key Mutational Sites | Asp28, Glu61, Ile66 | Asp28, Glu61, Ala63 |
| Drug Resistance | TMC207 resistance via mutations | TMC207 resistance via mutations |
| ATP Synthase Regulation | C-terminal α extension | C-terminal α extension |
KEGG: mlb:MLBr01140