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Defining Substrate Specificities for Lipase and Phospholipase Candidates
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Defining Substrate Specificities for Lipase and Phospholipase Candidates

Published on: November 23, 2016

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Structure of bacterial phospholipid transporter MlaFEDB with substrate bound

Nicolas Coudray1,2, Georgia L Isom1, Mark R MacRae1

  • 1Department of Cell Biology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, United States.

Elife
|November 25, 2020
PubMed

Insights

The MlaFEDB ABC transporter structure reveals a pathway for phospholipid transport in bacteria, crucial for outer membrane integrity and antibiotic resistance. This finding offers insights into bacterial cell envelope maintenance.

Area of Science:

  • Microbiology
  • Structural Biology
  • Biochemistry

Background:

  • Phospholipid transport is vital for maintaining the outer membrane barrier in double-membraned bacteria.
  • This barrier is essential for bacterial virulence and antibiotic resistance.
  • The Mla (multiple lipid-binding) system, including the MlaFEDB ABC transporter, is implicated in phospholipid trafficking.

Purpose of the Study:

  • To determine the structure of the inner-membrane MlaFEDB complex.
  • To elucidate the mechanism of phospholipid transport mediated by MlaFEDB.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) was used to determine the structure of MlaFEDB.
  • The structure was resolved at 3.05 Å resolution.

Main Results:

  • The cryo-EM structure of MlaFEDB was determined, revealing distant evolutionary relationships to LPS, MacAB, and eukaryotic ABCA/ABCG transporters.
  • A continuous transport pathway was identified from the MlaE substrate-binding site through MlaD to the periplasm.
  • Two phospholipid molecules were found bound to MlaFEDB, suggesting multi-substrate transport per cycle.

Conclusions:

  • The structure provides mechanistic insights into substrate recognition and transport by MlaFEDB.
  • This work advances our understanding of phospholipid homeostasis and outer membrane biogenesis in bacteria.
  • The findings may have implications for developing new antimicrobial strategies targeting bacterial membrane integrity.
Keywords:
E. colibacterial outer membranecryo-EMlipid transportmla pathwaymolecular biophysicsstructural biology

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