Crystal structure of the outer membrane active transporter FepA from Escherichia coli

Integral outer membrane receptors for iron chelates and vitamin B-12 carry out specific ligand transport against a concentration gradient. Energy for active transport is obtained from the proton-motive force of the inner memb rane through physical interaction with TonB-ExbB-ExbD, an inner membrane co mplex. Here we report the crystal structure of an active transport, outer m embrane receptor at 2.4 Angstrom resolution. Two distinct functional domain s are revealed: (i) a 22-stranded beta-barrel that spans the outer membrane and contains large extracellular loops which appear to function in ligand binding; and (ii) a globular N-terminal domain that folds into the barrel p ore, inhibiting access to the periplasm and contributing two additional loo ps for potential ligand binding. These loops could provide a signaling path way between the processes of ligand recognition and TonB-mediated transport . The blockage of the pore suggests that the N-terminal domain must undergo a conformational rearrangement to allow ligand transport into the periplas m.