The crystal structure of an inward-facing, nucleotide-free folate energy-coupling factor transporter from Lactobacillus brevis at a resolution of 3 A suggests a transport model that involves a substantial conformational change of the substrate-specific binding protein, FolT. The ATP-binding cassette (ABC) transporters harness the energy of ATP binding and hydrolysis for substrate transport across the cell membrane. Two papers in this issue of Nature report the X-ray crystal structures of two members of a recently recognized ABC transporter superfamily, the energy-coupling factor (ECF) transporters involved in vitamin and micronutrient uptake in prokaryotes. Both molecules are from Lactobacillus brevis. Peng Zhang and colleagues have solved the structure of a folate ECF transporter, and Yigong Shi and colleagues have solved the structure of an ECF transporter that is believed to be specific for hydroxymethyl pyrimidine. The structures enable the authors to propose a plausible working model for the transport cycle of the ECF transporters. There are no mammalian homologues for the S protein components of ECF transporters, and the molecules have notably high substrate-binding affinity, suggesting that they are worth investigating as potential targets for much-needed new antibiotics. ATP-binding cassette (ABC) transporters, composed of importers and exporters, form one of the biggest protein superfamilies that transport a variety of substrates across the membrane, powered by ATP hydrolysis. Most ABC transporters are composed of two transmembrane domains and two cytoplasmic nucleotide-binding domains. Also, importers from prokaryotes usually have extra solute-binding proteins in the periplasm that are responsible for the binding of substrates1,2. Structures of importers have been reported that suggested a two-state model for the transport mechanism3,4,5,6,7,8,9,10,11. Energy-coupling factor (ECF) transporters belong to a new class of ATP-binding cassette importers. Each ECF transporter comprises an energy-coupling module consisting of a transmembrane T protein (EcfT), two nucleotide-binding proteins (EcfA and EcfA′), and another transmembrane substrate-specific binding S protein12,13,14 (EcfS). Despite the similarities with ABC transporters, ECF transporters have different organizational and functional properties. The lack of solute-binding proteins in ECF transporters differentiates them clearly from the canonical ABC importers15. Previously reported structures of the EcfS proteins RibU and ThiT clearly demonstrated the binding site of substrate riboflavin and thiamine, respectively16,17. However, the organization of the four different components and the transport mechanism of ECF transporters remain unknown. Here we present the structure of an intact folate ECF transporter from Lactobacillus brevis at a resolution of 3 A. This structure was captured in an inward-facing, nucleotide-free conformation with no bound substrate. The folate-binding protein FolT is nearly parallel to the membrane and is bound almost entirely by EcfT, which adopts an L shape and connects to EcfA and EcfA′ through two coupling helices. Two conserved XRX motifs from the coupling helices of EcfT have a vital role in energy coupling by docking into EcfA–EcfA′. We propose a transport model that involves a substantial conformational change of FolT.