How phospholipids are trafficked between the bacterial inner and outer membranes through the intervening hydrophilic space of the periplasm is not known. Here we report that members of the mammalian cell entry (MCE) protein family form structurally diverse hexameric rings and barrels with a central channel capable of mediating lipid transport. The E. coli MCE protein, MlaD, forms a ring as part of a larger ABC transporter complex in the inner membrane, and employs a soluble lipid-binding protein to ferry lipids between MlaD and an outer membrane protein complex. In contrast, EM structures of two other E. coli MCE proteins show that YebT forms an elongated tube consisting of seven stacked MCE rings, and PqiB adopts a syringe-like architecture. Both YebT and PqiB create channels of sufficient length to span the entire periplasmic space. This work reveals diverse architectures of highly conserved protein-based channels implicated in the transport of lipids between the inner and outer membranes of bacteria and some eukaryotic organelles.
HIGHLIGHTS
MCE proteins adopt diverse architectures for transporting lipids across the bacterial periplasm
Cryo-EM and X-ray structures reveal how the MlaFEDB complex, along with MlaC, might shuttle lipids across the periplasm
3.9 Å cryo-EM structure of PqiB reveals a syringe-like architecture with a continuous central channel
YebT forms a a segmented tube-like structure, and YebT and PqiB are poised to directly link the inner and outer membranes to facilitate lipid transport.
View the discussion thread.