Abstract: Series 112, Lecture 4

The Harvey Lectures Series 112 (2016—2017)

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Lecture #4: Thursday, February 16, 2017 — Watch Video of Lecture

Ancient Challenge, New Physiology, Weird Ion Channel: Fluoride Resistance in Microorganisms

Chris Miller, PhD

Chris Miller, PhD

Professor of Biochemistry
Investigator, Howard Hughes Medical Institute

Howard Hughes Medical Institute, Brandeis University

Waltham, Massachusetts

Dr Miller's Website

Until a few years ago, the F- ion was widely considered utterly irrelevant to membrane biology — an orphan halide that does not participate in any membrane-transport phenomena. This view was overturned by Ronald Breaker's 2012 discovery of F--specific riboswitches in many bacterial genomes, genetic elements that control expression of novel membrane proteins that function as F- exporters. These exporters are found in two separate, phylogenetically unrelated classes: energy-consuming F-/H+ antiporters of the CLC superfamily found exclusively in bacteria, and thermodynamically passive “Fluc-family ” ion channels found in prokaryotes, eukaryotic microorganisms, plants, and primitive marine animals, but not in vertebrates.

The physiological purpose of F- exporters, at least in microbes, is to protect these organisms from inhibition of certain key metabolic enzymes by F- ion, which is ubiquitous in the aqueous biosphere, and has been so since the beginnings of evolutionary time. F- export proteins are inorganic analogues of multidrug resistance transporters, long known to resist toxicity of the myriad small organic toxins that pervade our environment. This lecture will discuss our current understanding — still primitive at this early stage — of F- resistance physiology implemented by the Fluc-type F- channels. The unusual chemical properties of F- ion explain why a passive ion channel can operate in a microbial context as an exporter to maintain a low cytoplasmic concentration of the halide anion, and the genomic organization of Fluc channels provides insights into evolution of the inverted structural repeats now commonly seen in the crystal structures of many transporters and ion channels. Finally, a recent high-resolution structure of a bacterial Fluc-type exporter shows some completely unexpected features of this unusual ion channel.