pH-dependent gating in a FocA formate channel
15.04.2011
Lü W, Du J, Wacker T, Gerbig-Smentek E, Andrade SL, Einsle O
Science. 2011, 332(6027):352-4.
Formate (HCOO-) is an important intermediate in a variety of metabolic pathways in microorganisms. Its transport across biological membranes is mediated by a pentameric integral membrane protein, the formate channel FocA. As a unique feature among known transport proteins, FocA switches its mode of operation from a passive export channel at high external pH to a secondary active symporter for formate and protons at low external pH.
Earlier structure determinations of FocA showed the high pH form, where all five protomers of the FocA pentamer were in an open conformation, representing the functional mode of passive channeling.
We were now able to obtain a crystal structure of FocA from Salmonella typhimurium at pH 4 that showed distinct changes in the N-termini of the peptide chains. While at high pH values all termini were disordered, they were now relocated to open or block transport in a concerted and cooperative action, leaving only one monomer in an open state, but two others half-closed and the remaining two fully closed. At this pH value FocA is supposed to act as an active importer and the passive channeling function should cease. This is in line with our electrophysiological studies that show that electrogenic formate uniport through FocA is well detectable, but ceases when the pH value drops below 5.1.
