8I8R

Cryo-EM Structure of OmpC3-MlaA Complex in MSP2N2 Nanodiscs

This is a non-PDB format compatible entry.

Summary for 8I8R

• Entry DOI: 10.2210/pdb8i8r/pdb
• EMDB information: 35250
• Descriptor: Outer membrane porin C, Intermembrane phospholipid transport system lipoprotein MlaA, (2~{R},4~{R},5~{R},6~{R})-6-[(1~{R})-1,2-bis(oxidanyl)ethyl]-2-[(2~{R},4~{R},5~{R},6~{R})-6-[(1~{R})-1,2-bis(oxidanyl)ethyl]-2-carboxy-2-[[(2~{R},3~{S},4~{R},5~{R},6~{R})-5-[[(3~{R})-3-dodecanoyloxytetradecanoyl]amino]-6-[[(2~{R},3~{S},4~{R},5~{R},6~{R})-3-oxidanyl-5-[[(3~{R})-3-oxidanyltetradecanoyl]amino]-4-[(3~{R})-3-oxidanyltetradecanoyl]oxy-6-phosphonooxy-oxan-2-yl]methoxy]-3-phosphonooxy-4-[(3~{R})-3-tetradecanoyloxytetradecanoyl]oxy-oxan-2-yl]methoxy]-5-oxidanyl-oxan-4-yl]oxy-4,5-bis(oxidanyl)oxane-2-carboxylic acid (3 entities in total)
• Functional Keywords: bacteria, outer membrane, phospholipid, lipid asymmetry, membrane protein, protein complex structure, channel, lipid transport
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 4
• Total formula weight: 148023.22

Authors

Yeow, J.,Luo, M.,Chng, S.S. (deposition date: 2023-02-05, release date: 2023-12-20, Last modification date: 2023-12-27)

Primary citation

Yeow, J.,Luo, M.,Chng, S.S.
Molecular mechanism of phospholipid transport at the bacterial outer membrane interface.
Nat Commun, 14:8285-8285, 2023

PubMed Abstract: The outer membrane (OM) of Gram-negative bacteria is an asymmetric lipid bilayer with outer leaflet lipopolysaccharides and inner leaflet phospholipids (PLs). This unique lipid asymmetry renders the OM impermeable to external insults, including antibiotics and bile salts. To maintain this barrier, the OmpC-Mla system removes mislocalized PLs from the OM outer leaflet, and transports them to the inner membrane (IM); in the first step, the OmpC-MlaA complex transfers PLs to the periplasmic chaperone MlaC, but mechanistic details are lacking. Here, we biochemically and structurally characterize the MlaA-MlaC transient complex. We map the interaction surfaces between MlaA and MlaC in Escherichia coli, and show that electrostatic interactions are important for MlaC recruitment to the OM. We further demonstrate that interactions with MlaC modulate conformational states in MlaA. Finally, we solve a 2.9-Å cryo-EM structure of a disulfide-trapped OmpC-MlaA-MlaC complex in nanodiscs, reinforcing the mechanism of MlaC recruitment, and highlighting membrane thinning as a plausible strategy for directing lipids for transport. Our work offers critical insights into retrograde PL transport by the OmpC-Mla system in maintaining OM lipid asymmetry.

PubMed: 38092770
DOI: 10.1038/s41467-023-44144-8

Experimental method

ELECTRON MICROSCOPY (2.93 Å)