Biophysical comparison of ATP-driven proton pumping mechanisms suggests a kinetic advantage for the rotary process depending on coupling ratio

TL;DR

This study compares ATP-driven proton pump mechanisms, revealing that rotary pumps with higher proton-to-ATP ratios have kinetic advantages, explaining their evolutionary preference under certain cellular conditions.

Contribution

The paper provides a systematic kinetic analysis showing rotary mechanisms outperform alternative mechanisms when the proton-to-ATP ratio exceeds one, offering insights into their evolutionary selection.

Findings

Rotary pumps with H+:ATP ratio > 1 are kinetically faster.

Alternating access pumps are simpler but less efficient at higher ratios.

The mechanism choice correlates with the proton coupling ratio.

Abstract

ATP-driven proton pumps, which are critical to the operation of a cell, maintain cytosolic and organellar pH levels within a narrow functional range. These pumps employ two very different mechanisms: an elaborate rotary mechanism used by V-ATPase H+ pumps, and a simpler alternating access mechanism used by P-ATPase H+ pumps. Why are two different mechanisms used to perform the same function? Systematic analysis, without parameter fitting, of kinetic models of the rotary, alternating access and other possible mechanisms suggest that, when the ratio of protons transported per ATP hydrolyzed exceeds one, the one-at-a-time proton transport by the rotary mechanism is faster than other possible mechanisms across a wide range of driving conditions. When the ratio is one, there is no intrinsic difference in the free energy landscape between mechanisms, and therefore all mechanisms can exhibit the same kinetic performance. To our knowledge all known rotary pumps have an H+:ATP ratio greater than one, and all known alternating access ATP-driven proton pumps have a ratio of one. Our analysis suggests a possible explanation for this apparent relationship between coupling ratio and mechanism. When the conditions under which the pump must operate permit a coupling ratio greater than one, the rotary mechanism may have been selected for its kinetic advantage. On the other hand, when conditions require a coupling ratio of one or less, the alternating access mechanism may have been selected for other possible advantages resulting from its structural and functional simplicity.