The TamB ortholog of <i>Borrelia burgdorferi</i> interacts with the β‐barrel assembly machine (BAM) complex protein BamA

Iqbal, Henna; Kenedy, Melisha R.; Lybecker, Meghan; Akins, Darrin R.

doi:10.1111/mmi.13492

Cited by 52 publications

(48 citation statements)

References 103 publications

(196 reference statements)

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“…More recently, in Borrelia burgdorferi , the TamB component of TAM was shown to interact directly with BamA and to be an essential component of the BAM complex 73 . Exactly how the BAM and TAM systems communicate with one another, how they decide their substrates, and what mechanistic role each may have in OMP biogenesis remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

The β-barrel assembly machinery in motion

2017

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In Gram-negative bacteria, the biogenesis of β-barrel outer membrane proteins is mediated by the β-barrel assembly machinery (BAM) complex. Over the past decade, structural and functional studies have collectively contributed to advancing our understanding of the BAM complex structure and function; however the exact mechanism remains elusive. In this Progress article, we discuss recent structural studies that have revealed that the accessory proteins may regulate essential unprecedented conformational changes within the core component BamA during function. We also review the mechanistic insights that have been gained from structural data, mutagenesis studies, molecular dynamics simulations, and explore two emerging models for BAM-mediated OMP biogenesis in bacteria.

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Section: Discussionmentioning

confidence: 99%

The β-barrel assembly machinery in motion

2017

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“…Multiple lines of evidence point to a similar exclusion mechanism at the second checkpoint in the OM, where periplasmic lipoproteins are blocked from "flipping" through the OM due to assumption of their final tertiary structure (57, 76, 92-94). The B. burgdorferi BAM protein BamA was shown to be at least indirectly involved in this process (134), and it remains to be determined if/how the other identified B. burgdorferi BAM complex proteins (56, 114), including the IM protein TamB (135), play a role in lipoprotein secretion. Recent work has shown that some Neisseria surface lipoproteins are secreted to the surface through the lumen of beta-barrel integral OM proteins (44), but homologs are missing from Borrelia genomes.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Spatial Analysis of the Borrelia burgdorferi Lipoproteome Reveals a Compartmentalization Bias toward the Bacterial Surface

et al. 2017

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The Lyme disease spirochete Borrelia burgdorferi is unique among bacteria in its large number of lipoproteins that are encoded by a small, exceptionally fragmented, and predominantly linear genome. Peripherally anchored in either the inner or outer membrane and facing either the periplasm or the external environment, these lipoproteins assume varied roles. A prominent subset of lipoproteins functioning as the apparent linchpins of the enzootic tick-vertebrate infection cycle have been explored as vaccine targets. Yet, most of the B. burgdorferi lipoproteome has remained uncharacterized. Here, we comprehensively and conclusively localize the B. burgdorferi lipoproteome by applying established protein localization assays to a newly generated epitope-tagged lipoprotein expression library and by validating the obtained individual protein localization results using a sensitive global mass spectrometry approach. The derived consensus localization data indicate that 86 of the 125 analyzed lipoproteins encoded by B. burgdorferi are secreted to the bacterial surface. Thirty-one of the remaining 39 periplasmic lipoproteins are retained in the inner membrane, with only 8 lipoproteins being anchored in the periplasmic leaflet of the outer membrane. The localization of 10 lipoproteins was further defined or revised, and 52 surface and 23 periplasmic lipoproteins were newly localized. Cross-referencing prior studies revealed that the borrelial surface lipoproteome contributing to the hostpathogen interface is encoded predominantly by plasmids. Conversely, periplasmic lipoproteins are encoded mainly by chromosomal loci. These studies close a gap in our understanding of the functional lipoproteome of an important human pathogen and set the stage for more in-depth studies of thus-far-neglected spirochetal lipoproteins.IMPORTANCE The small and exceptionally fragmented genome of the Lyme disease spirochete Borrelia burgdorferi encodes over 120 lipoproteins. Studies in the field have predominantly focused on a relatively small number of surface lipoproteins that play important roles in the transmission and pathogenesis of this global human pathogen. Yet, a comprehensive spatial assessment of the entire borrelial lipoproteome has been missing. The current study newly identifies 52 surface and 23 periplasmic lipoproteins. Overall, two-thirds of the B. burgdorferi lipoproteins localize to the surface, while outer membrane lipoproteins facing the periplasm are rare. This analysis underscores the dominant contribution of lipoproteins to the spirochete's rather complex and adaptable host-pathogen interface, and it encourages further functional exploration of its lipoproteome.KEYWORDS cell envelope, lipoproteins, localization, membrane biogenesis, membrane proteins, outer membrane, protein secretion, proteomics, spirochetes, surface proteins

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“…TamA is found throughout the Proteobacteria , and TamB has an even broader distribution through Gram‐negative bacterial lineages (Heinz et al ., ). Recent studies with Borrelia burgdorferi suggest that in organisms that lack a TamA, TamB interacts instead with BamA (Iqbal et al ., ; Stubenrauch et al ., ). Phylogenetic analyses suggested a model wherein the TAM evolved originally from a complex of BamA and TamB, with a subsequent gene duplication of bamA giving rise to a second Omp85 sequence in the genome, ultimately evolving to become TamA (Heinz et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Structural basis for substrate selection by the translocation and assembly module of the β‐barrel assembly machinery

Bamert

Lundquist

Hwang

et al. 2017

Molecular Microbiology

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The assembly of proteins into bacterial outer membranes is a key cellular process that we are only beginning to understand, mediated by the β-barrel assembly machinery (BAM). Two crucial elements of that machinery are the core BAM complex and the translocation and assembly module (TAM), with each containing a member of the Omp85 superfamily of proteins: BamA in the BAM complex, TamA in the TAM. Here, we used the substrate protein FimD as a model to assess the selectivity of substrate interactions for the TAM relative to those of the BAM complex. A peptide scan revealed that TamA and BamA bind the β-strands of FimD, and do so selectively. Chemical cross-linking and molecular dynamics are consistent with this interaction taking place between the first and last strand of the TamA barrel domain, providing the first experimental evidence of a lateral gate in TamA: a structural element implicated in membrane protein assembly. We suggest that the lateral gates in TamA and BamA provide different environments for substrates to engage, with the differences observed here beginning to address how the TAM can be more effective than the BAM complex in the folding of some substrate proteins.

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The TamB ortholog of Borrelia burgdorferi interacts with the β‐barrel assembly machine (BAM) complex protein BamA

Cited by 52 publications

References 103 publications

The β-barrel assembly machinery in motion

The β-barrel assembly machinery in motion

Comprehensive Spatial Analysis of the Borrelia burgdorferi Lipoproteome Reveals a Compartmentalization Bias toward the Bacterial Surface

Structural basis for substrate selection by the translocation and assembly module of the β‐barrel assembly machinery

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