Formation of a chloride-conducting state in the Maltose ATP-Binding Cassette (ABC) transporter [Protein Structure and Folding]

April 7th, 2016 by Carlson, M. L., Bao, H., Duong, F.

ABC transporters use an alternating access mechanism to move substrates across cellular membranes. This mode of transport ensures the selective passage of molecules while preserving membrane impermeability. The crystal structures of MalFGK2, inward- and outward-facing, show that the transporter is sealed against ions and small molecules. It has yet to be determined whether membrane impermeability is maintained when MalFGK2 cycles between these two conformations. Through the use of a mutant that resides in intermediate conformations close to the transition state, we demonstrate that not only is chloride conductance occurring, but also to a degree large enough to compromise cell viability. Introduction of mutations in the periplasmic gate lead to the formation of a channel that is quasi-permanently open. MalFGK2 must therefore stay away from these ion-conducting conformations in order to preserve the membrane barrier; otherwise, a few mutations that increase access to the ion-conducting states are enough to convert an ABC transporter into a channel.