Functional and evolutional implications of natural channel-enzyme fusion proteins.

Abstract

Channeling of ions or substrates across membranes and enzymatic activity are two highly distinct biochemical concepts. They are usually studied by different research groups, which focus on either subject. Nature has provided a challenge for specialized scientists by fusing genes coding for a transmembrane channel domain with an enzyme domain. There are examples of fusion proteins consisting of an N-terminal ion channel or sensor and a C-terminal, cytosolic kinase domain (or other enzymes involved in signaling) of which either domain may influence the functionality of the other. The physiological role of such fusions may reside in coupling ion flux or membrane potential sensing to cellular responses or vice-versa. Other examples can be found in metabolism. We have identified and characterized an ar-senite-conducting aquaglyceroporin carrying a C-terminal ar-senate reductase domain. Here, a function in the detoxification of arsenic is obvious, with the enzyme domain generating the substrate for the channel domain, which immediately shuttles the toxic metabolite out of the cell. We see two advantages in this latter concept: lowering of the cellular toxicity due to rapid release of the substrate and energetic coupling of the reaction enthalpy to extrusion due to high local substrate gradients. In this overview, we summarize and discuss the current view on functional and physiological aspects of channel/enzyme fusion proteins.