Phospholipid transport to the bacterial outer membrane through an envelope-spanning bridge
Benjamin F Cooper1, Robert Clark2, Anju Kudhail1
1Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, UK.
Biorxiv : the Preprint Server for Biology
|October 24, 2023
Summary
YhdP protein transports phospholipids across the Gram-negative bacterial cell envelope. This newly discovered mechanism involves YhdP forming a bridge, facilitating essential lipid transport for outer membrane biogenesis and bacterial survival.
Area of Science:
- Microbiology
- Structural Biology
- Biochemistry
Background:
- Gram-negative bacteria possess an outer membrane crucial for pathogenesis and antibiotic resistance.
- Outer membrane biogenesis depends on phospholipid transport across the cell envelope.
- The mechanism of YhdP-mediated phospholipid transport remained largely unknown.
Approach:
- Utilized AlphaFold for structural prediction of YhdP.
- Employed negative stain electron microscopy to determine YhdP structure and size.
- Conducted molecular dynamics simulations and in vivo bacterial growth assays.
- Performed in vivo crosslinking experiments to identify transported substrates.
Key Points:
- YhdP forms an elongated, 60 β-strand assembly with a continuous hydrophobic groove, approximately 250 Å long.
- Helical regions at YhdP's termini may anchor it to the inner and outer membranes.
- In vivo crosslinking captured phosphate-containing substrates within the YhdP groove, confirming phospholipid transport.
- Molecular dynamics simulations showed lipids entering the YhdP groove from the inner membrane.
Conclusions:
- YhdP acts as a bridge across the bacterial cell envelope.
- The hydrophobic groove of YhdP facilitates phospholipid transport to the outer membrane.
- This mechanism is vital for outer membrane biogenesis in Gram-negative bacteria.
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