RT Journal Article
SR Electronic
T1 Structure of an endogenous mycobacterial MCE lipid transporter
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.12.08.519548
DO 10.1101/2022.12.08.519548
A1 Chen, James
A1 Fruhauf, Alice
A1 Fan, Catherine
A1 Ponce, Jackeline
A1 Ueberheide, Beatrix
A1 Bhabha, Gira
A1 Ekiert, Damian C.
YR 2022
UL http://biorxiv.org/content/early/2022/12/08/2022.12.08.519548.abstract
AB Mycobacterium tuberculosis (Mtb) infects human macrophages, where it scavenges nutrients for survival. The Mammalian Cell Entry (MCE) proteins are important virulence factors implicated in import of nutrients such as fatty acids from the host, but their structures and mechanisms remain unknown. Here we report the high-resolution structure of the endogenous Mce1 transporter from Mycobacterium smegmatis, a non-pathogenic relative of Mtb. Ten distinct proteins assemble into an elongated complex, long enough to span the cell envelope. A unique helical needle creates a curved hydrophobic tunnel for lipid transport across the periplasm. Combining cryo-EM and AlphaFold2, we identify a previously unknown subunit of the Mce1 complex, which we name LucB. Our data lead to a structural model for Mce1-mediated fatty acid import in mycobacteria.One-sentence Summary Cryo-EM structure reveals how a major mycobacterial virulence factor, Mce1, assembles to transport fatty acids across the cell envelope.Competing Interest StatementThe authors have declared no competing interest.