Proton transport drives allosteric conformational changes in the MmpL3 transporter.

Protonation of Asp256 in MmpL3 induces open conformations linked to substrate translocation in Mycobacterium smegmatis.

• Why it matters: Understanding how proton-driven dynamics regulate MmpL3 function is crucial for developing targeted therapies against drug-resistant tuberculosis.
• What they did: Molecular dynamics simulations of MmpL3 examined the effects of protonation at Asp256 and Asp645 on conformational states and water accessibility, focusing on TMM binding.
• The result: Protonation of Asp256 promotes open dyad conformations and increased water access, supporting a sequential protonation model that couples conformational changes to substrate transport.