9N8X

Intermembrane lipid transport complex LetAB from Escherichia coli (Composite model corresponding to Map 2)

Summary for 9N8X

• Entry DOI: 10.2210/pdb9n8x/pdb
• EMDB information: 49152
• Descriptor: Intermembrane transport protein YebS, Intermembrane transport protein YebT, ZINC ION, ... (4 entities in total)
• Functional Keywords: lipid transporter, outer membrane integrity, mce system, metal-binding protein, intermembrane complex, lipid transport
• Biological source: Escherichia coli str. K-12 substr. MG1655; More
• Total number of polymer chains: 7
• Total formula weight: 621923.79

Authors

Santarossa, C.C.,Bhabha, G.,Ekiert, D.C. (deposition date: 2025-02-10, release date: 2025-11-05)

Primary citation

Santarossa, C.C.,Li, Y.,Yousef, S.,Hasdemir, H.S.,Rodriguez, C.C.,Haase, M.B.,Baek, M.,Coudray, N.,Pavek, J.G.,Focke, K.N.,Silverberg, A.L.,Bautista, C.,Yeh, J.,Marty, M.T.,Baker, D.,Tajkhorshid, E.,Ekiert, D.C.,Bhabha, G.
LetA defines a structurally distinct transporter family involved in lipid trafficking.
Biorxiv, 2025

PubMed Abstract: Membrane transport proteins translocate diverse cargos, ranging from small sugars to entire proteins, across cellular membranes. A few structurally distinct protein families have been described that account for most of the known membrane transport processes. However, many membrane proteins with predicted transporter functions remain uncharacterized. We determined the structure of LetAB, a phospholipid transporter involved in outer membrane integrity, and found that LetA adopts a distinct architecture that is structurally and evolutionarily unrelated to known transporter families. LetA functions as a pump at one end of a ~225 Å long tunnel formed by its binding partner, MCE protein LetB, creating a pathway for lipid transport between the inner and outer membranes. Unexpectedly, the LetA transmembrane domains adopt a fold that is evolutionarily related to the eukaryotic tetraspanin family of membrane proteins, including TARPs and claudins. LetA has no detectable homology to known transport proteins, and defines a new class of membrane transporters. Through a combination of deep mutational scanning, molecular dynamics simulations, AlphaFold-predicted alternative states, and functional studies, we present a model for how the LetA-like family of membrane transporters may use energy from the proton-motive force to drive the transport of lipids across the bacterial cell envelope.

PubMed: 40166208
DOI: 10.1101/2025.03.21.644421

Experimental method

ELECTRON MICROSCOPY (3.5 Å)