Proton Transport Mechanism of M2 Proton Channel Studied by Laser-Induced pH Jump

摘要

The M2 proton transport channel of the influenza virus A is an important model system because it conducts protons with high selectivity and unidirectionally when activated at low pH, despite the relative simplicity of its structure. Although it has been studied extensively, the molecular details of the pH-dependent gating and proton conductance mechanisms are incompletely understood. We report direct observation of the M2 proton channel activation process using a laser-induced pH jump coupled with tryptophan fluorescence as a probe. Biphasic kinetics is observed, with the fast phase corresponding to the His37 protonation, and the slow phase associated with the subsequent conformation change. Unusually fast His37 protonation was observed (2.0 × 10~(10) M~(-1) s~(-1)), implying the existence of proton collecting antennae for expedited proton transport. The conformation change (4 × 10~3 s~(-1)) was about 2 orders of magnitude slower than protonation at endosomal pH, suggesting that a transporter model is likely not feasible.