Formate uptake/efflux permease, FocA.  It catalyzes bidirectional transport, has a pentameric aquaporin-like (TC# 1.A.8) structure, and may function by a channel-type mechanism (Falke et al., 2009; Wang et al. 2009). The structure at 2.25 Å resolution has been determined (Wang et al., 2009).  The protein is encoded in an operon with pyruvate-formate lyase, PflB.  A pyruvate:formate antiport mechanism has been suggested (Moraes and Reithmeier 2012). The C-terminal 6 aas are required for formate transport, but not for homopentamer formation (Hunger et al. 2017).  The N-terminus of FocA interacts with PflB, and this interaction is essential for optimal formate translocation (Doberenz et al. 2014). In fact, the GREs, TdcE and PflB, interact with the FNT channel protein, probably to control formate translocation by FocA (Falke et al. 2016). The lipophilic constrictions of FocA mainly act as barriers to isolate the central histidine from the aqueous bulk, preventing protonation via proton wires. Thus, an FNT transport model is supported in which the central histidine is uncharged, and weak acid substrate anion protonation occurs in the vestibule regions of the transporter before passing the constrictions (Schmidt and Beitz 2021). An interplay between the conserved pore residues Thr-91 and His-209 controls formate translocation through the FocA channel (Kammel et al. 2022). T91 is essential for formate permeation in both directions; however, it is particularly important to allow anion efflux. H209 is essential for formate uptake by FocA, strongly suggesting that protonation-deprotonation of this residue plays a role in formate uptake. These observations substantiate the premise that efflux and influx of formate by FocA are mechanistically distinct processes that are controlled by the interplay between T91 and H209 (Kammel et al. 2022).