pH-Dependent Gating in a FocA Formate Channel

Abstract

The formate transporter FocA was described to switch its mode of operation from a passive export channel at high external pH to a secondary active formate/H+ importer at low pH. The crystal structure of Salmonella typhimurium FocA at pH 4.0 shows that this switch involves a major rearrangement of the amino termini of individual protomers in the pentameric channel. The amino-terminal helices open or block transport in a concerted, cooperative action that indicates how FocA is gated in a pH-dependent way. Electrophysiological studies show that the protein acts as a specific formate channel at pH 7.0 and that it closes upon a shift of pH to 5.1. Many enterobacterial species grow byanaerobic mixed-acid fermentation,whereby pyruvate, the end product of glycolysis, is converted to acetyl–coenzymeA and formate by a pyruvate:formate lyase (PFL) rather than being oxidized to yield CO2 as is the case in mitochondria (1). This process releases one-third of the carbon atom content of carbohydrates as formate, which, if left to accumulate in the cyto-plasm, would potentially lead to critical acidifica