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Cited by 8Bacterial Genetics and BiotechnologyLipid Membrane Structure and BehaviorBacterial Infections and Vaccines

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A comparative analysis of lipoprotein transport proteins: LolA and LolB from Vibrio cholerae and LolA from Porphyromonas gingivalis

Open access
Jaiman, Deepika, Nagampalli, Raghavendra, Persson, Karina·2023·Scientific Reports
DOI 10.1038/s41598-023-33705-yPMC PMC10126205

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Abstract

In Gram-negative bacteria, N-terminal lipidation is a signal for protein trafficking from the inner membrane (IM) to the outer membrane (OM). The IM complex LolCDE extracts lipoproteins from the membrane and moves them to the chaperone LolA. The LolA-lipoprotein complex crosses the periplasm after which the lipoprotein is anchored to the OM. In γ-proteobacteria anchoring is assisted by the receptor LolB, while a corresponding protein has not been identified in other phyla. In light of the low sequence similarity between Lol-systems from different phyla and that they may use different Lol components, it is crucial to compare representative proteins from several species. Here we present a structure–function study of LolA and LolB from two phyla: LolA from Porphyromonas gingivalis (phylum bacteroidota), and LolA and LolB from Vibrio cholerae (phylum proteobacteria). Despite large sequence differences, the LolA structures are very similar, hence structure and function have been conserved throughout evolution. However, an Arg-Pro motif crucial for function in γ-proteobacteria has no counterpart in bacteroidota. We also show that LolA from both phyla bind the antibiotic polymyxin B whereas LolB does not. Collectively, these studies will facilitate the development of antibiotics as they provide awareness of both differences and similarities across phyla.

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Figures

Figure 1 Lipidation and transport of lipoproteins. The prelipoprotein (LP) is transported over the IM where it is diacylated by the enzyme Lgt. Next the signal peptide is removed by the signal peptidase LspA. A third acyl chain is added to the N-terminal cysteine (in γ-proteobacteria) by the enzyme Lnt. The lipoprotein recognized by the LolCDE complex, is transported to the chaperone protein LolA, which in turn will deliver it to LolB at the OM (in γ-proteobacteria). The figure was created with BioRender.com.
Figure 1 Lipidation and transport of lipoproteins. The prelipoprotein (LP) is transported over the IM where it is diacylated by the enzyme Lgt. Next the signal peptide is removed by the signal peptidase LspA. A third acyl chain is added to the N-terminal cysteine (in γ-proteobacteria) by the enzyme Lnt. The lipoprotein recognized by the LolCDE complex, is transported to the chaperone protein LolA, which in turn will deliver it to LolB at the OM (in γ-proteobacteria). The figure was created with BioRender.com.CC BY · PubMed Central
Figure 2 The overall structures of LolA and LolB. (a) LolA from P. gingivalis (LolA-PG), (b) LolA (LolA-VC) and (c) LolB from V. cholerae (LolB-VC). The LolA-PG and LolA-VC structures (ribbon drawings) fold as a 12 β-strand open barrel with three α-helices. LolB-VC comprises an 11 stranded open β-barrel with three helices. A conserved proline located between helix α2 and α3 is shown as a stick model in all three proteins. The β-strands and loops are depicted in blue and the helices in green. (d–f) The solvent accessible part of the binding clefts were calculated with CASTp48 and are illustrated in orange. The cleft in LolA-PG is the most accessible with a volume of 36 Å3. The clefts of LolA-VC and LolB-VC are more scattered and comprise 0.15 and 11 Å3 respectively.
Figure 2 The overall structures of LolA and LolB. (a) LolA from P. gingivalis (LolA-PG), (b) LolA (LolA-VC) and (c) LolB from V. cholerae (LolB-VC). The LolA-PG and LolA-VC structures (ribbon drawings) fold as a 12 β-strand open barrel with three α-helices. LolB-VC comprises an 11 stranded open β-barrel with three helices. A conserved proline located between helix α2 and α3 is shown as a stick model in all three proteins. The β-strands and loops are depicted in blue and the helices in green. (d–f) The solvent accessible part of the binding clefts were calculated with CASTp48 and are illustrated in orange. The cleft in LolA-PG is the most accessible with a volume of 36 Å3. The clefts of LolA-VC and LolB-VC are more scattered and comprise 0.15 and 11 Å3 respectively.CC BY · PubMed Central
Figure 3 A comparison of the binding clefts in LolA. (a) In γ-proteobacteria, such as V. cholerae, an Arg-Pro motif (Arg59 and Pro60 in LolA-VC) is conserved. In E. coli the motif has been shown to be important for the interaction with LolB and the transfer of lipoproteins. With no binding partner bound in the cleft of LolA-VC Arg59 hydrogen bonds to main chain atoms at the end of α1 and of α3. (b) In LolA-PG the position equivalent to Arg59 is occupied by Gly75. The space that is filled by the Arg59 side chain in LolA-VC is filled with Leu41 in LolA-PG. (c) Overlay of LolA-EC in blue and LolA-PG in pink showing the similar size and shape of their cavities.
Figure 3 A comparison of the binding clefts in LolA. (a) In γ-proteobacteria, such as V. cholerae, an Arg-Pro motif (Arg59 and Pro60 in LolA-VC) is conserved. In E. coli the motif has been shown to be important for the interaction with LolB and the transfer of lipoproteins. With no binding partner bound in the cleft of LolA-VC Arg59 hydrogen bonds to main chain atoms at the end of α1 and of α3. (b) In LolA-PG the position equivalent to Arg59 is occupied by Gly75. The space that is filled by the Arg59 side chain in LolA-VC is filled with Leu41 in LolA-PG. (c) Overlay of LolA-EC in blue and LolA-PG in pink showing the similar size and shape of their cavities.CC BY · PubMed Central
Figure 4 Electrostatic representation of the opening of the hydrophobic cavity of LolA and LolB from different bacteria. (a) The hydrophobic cavity of LolA-EC is lined with negatively charged residues. The cavity of LolB-EC is on the other hand predominantly lined with positively charged residues. (b) LolA-VC and LolB-VC have similar surface charge distribution. (c) The hydrophobic cavity of LolA-PG is similarly lined with negatively charged residues. For clarity the helices filling the cavities are depicted as ribbons in green.
Figure 4 Electrostatic representation of the opening of the hydrophobic cavity of LolA and LolB from different bacteria. (a) The hydrophobic cavity of LolA-EC is lined with negatively charged residues. The cavity of LolB-EC is on the other hand predominantly lined with positively charged residues. (b) LolA-VC and LolB-VC have similar surface charge distribution. (c) The hydrophobic cavity of LolA-PG is similarly lined with negatively charged residues. For clarity the helices filling the cavities are depicted as ribbons in green.CC BY · PubMed Central
Figure 5 Chemical structures of the antibacterial molecules polymyxin B and A22. (a) The antibiotic polymyxin B and (b) the inhibitor A22.
Figure 5 Chemical structures of the antibacterial molecules polymyxin B and A22. (a) The antibiotic polymyxin B and (b) the inhibitor A22.CC BY · PubMed Central

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Metadata

Authors
Jaiman, D., Nagampalli, R., & Persson, K.
Affiliations
Umeå Centre for Microbial Research (SE)
Corresponding author
Persson, Karina
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2023-04-24
Volume
13
Issue
1
Pages
6605-6605
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-023-33705-y
PMC
PMC10126205
OpenAlex
W4366829709
Cited by
8
References
48
Citations by year
2026: 4 · 2024: 3 · 2023: 1
FWCI
1.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
  • Desy publication database (The Deutsches Elektronen-Synchrotron) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron)
Funders
  • Vetenskapsrådet (2007-08673, 2016-05009)
  • Stiftelsen Lars Hiertas Minne
  • Medical faculty, Umeå University
  • Umea University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Immunology and Microbiology › Microbiology › Bacterial Infections and Vaccines
Keywords
lipoprotein transport, LOLA, Gram-negative bacteria, Vibrio cholerae, Porphyromonas gingivalis, periplasmic chaperone
MeSH terms
Bacterial Outer Membrane Proteins, Carrier Proteins, Cell Membrane, Escherichia coli, Lipoproteins, Vibrio cholerae, Porphyromonas gingivalis, Protein Transport, Escherichia coli Proteins, Periplasmic Binding Proteins

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