Title: LetB Structure Reveals a Tunnel for Lipid Transport across the Bacterial Envelope
Author: Georgia L. Isom, Nicolas Coudray, Mark R. MacRae, Collin T. McManus, Damian C. Ekiert, Gira Bhabha
Abstract: Gram-negative bacteria are surrounded by an outer membrane composed of phospholipidsand lipopolysaccharide, which acts as a barrier and contributes to antibiotic resistance.The systems that mediate phospholipid trafficking across the periplasm, such as MCE(Mammalian Cell Entry) transporters, have not been well characterized. Our ~3.5 cryo-EM structure of the E. coli MCE protein LetB reveals an ~0.6 megadalton complex that consists of seven stackedrings, with a central hydrophobic tunnel sufficiently long to span the periplasm.Lipids bind inside the tunnel, suggesting that it functions as a pathway for lipidtransport. Cryo-EM structures in the open and closed states reveal a dynamic tunnellining, with implications for gating or substrate translocation. Our results supporta model in which LetB establishes a physical link between the two membranes and createsa hydrophobic pathway for the translocation of lipids across the periplasm.