scholarly journals Evolution of Environmentally-Enforced, Repeat Protein Topology in the Outer Membrane

2018 ◽  
Author(s):  
Meghan Whitney Franklin ◽  
Sergey Nepomnyachiy ◽  
Ryan Feehan ◽  
Nir Ben-Tal ◽  
Rachel Kolodny ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Repeat Protein ◽  
Protein Topology ◽  
Beta Barrel ◽  
Domain Duplication ◽  
Folding Pathways ◽  
Number Variation ◽  
Beta Barrels ◽  
Beta Hairpin ◽  
Evolutionary Story

AbstractOuter membrane beta barrels (OMBBs) are the proteins on the surface of Gram negative bacteria. These proteins have diverse functions but only a single topology, the beta barrel. It has been suggested that this common fold is a repeat protein with the repeating unit of a beta hairpin. By grouping structurally solved OMBBs by sequence, a detailed evolutionary story unfolds. A strand-number based pathway manifests with progression from a primordial 8-stranded barrel to 16-stranded and then to 18-stranded barrels. The transitions from 16- to 18-stranded barrels show mechanisms of strand number variation without domain duplication, such as a loop to hairpin transition. This indicates that repeat protein topology can be perpetuated without genetic duplication likely because the topology is being enforced by the membrane environment. Moreover, we find the evolutionary trace is particularly prominent in the C-terminal half of OMBBs which may be relevant to understanding OMBB folding pathways.

scholarly journals Evolutionary pathways of repeat protein topology in bacterial outer membrane proteins

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Meghan Whitney Franklin ◽  
Sergey Nepomnyachyi ◽  
Ryan Feehan ◽  
Nir Ben-Tal ◽  
Rachel Kolodny ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Integrated Approach ◽  
Hydrophobic Membrane ◽  
Repeat Protein ◽  
Protein Topology ◽  
Domain Duplication ◽  
Bacterial Outer Membrane ◽  
Evolutionary Pathways

Outer membrane proteins (OMPs) are the proteins in the surface of Gram-negative bacteria. These proteins have diverse functions but a single topology: the β-barrel. Sequence analysis has suggested that this common fold is a β-hairpin repeat protein, and that amplification of the β-hairpin has resulted in 8–26-stranded barrels. Using an integrated approach that combines sequence and structural analyses, we find events in which non-amplification diversification also increases barrel strand number. Our network-based analysis reveals strand-number-based evolutionary pathways, including one that progresses from a primordial 8-stranded barrel to 16-strands and further, to 18-strands. Among these pathways are mechanisms of strand number accretion without domain duplication, like a loop-to-hairpin transition. These mechanisms illustrate perpetuation of repeat protein topology without genetic duplication, likely induced by the hydrophobic membrane. Finally, we find that the evolutionary trace is particularly prominent in the C-terminal half of OMPs, implicating this region in the nucleation of OMP folding.

scholarly journals Author response: Evolutionary pathways of repeat protein topology in bacterial outer membrane proteins

2018 ◽  
Author(s):  
Meghan Whitney Franklin ◽  
Sergey Nepomnyachyi ◽  
Ryan Feehan ◽  
Nir Ben-Tal ◽  
Rachel Kolodny ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Author Response ◽  
Repeat Protein ◽  
Protein Topology ◽  
Bacterial Outer Membrane ◽  
Evolutionary Pathways

scholarly journals The role of BamA in the biogenesis of beta-barrel membrane proteins

2014 ◽  
Vol 70 (a1) ◽  
pp. C578-C578
Author(s):  
Nicholas Noinaj ◽  
Adam Kuszak ◽  
Curtis Balusek ◽  
JC Gumbart ◽  
Petra Lukacik ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Crystal Structures ◽  
Outer Membrane Proteins ◽  
Hydrophobic Surface ◽  
Md Simulations ◽  
Structural Features ◽  
Bam Complex ◽  
Beta Barrel

Beta-barrel membrane proteins are essential for nutrient import, signaling, motility, and survival. In Gram-negative bacteria, the beta-barrel assembly machinery (BAM) complex is responsible for the biogenesis of beta-barrel outer membrane proteins (OMPs), with homologous complexes found in mitochondria and chloroplasts. Despite their essential roles, exactly how these OMPs are formed remains unknown. The BAM complex consists of a central and essential component called BamA (an OMP itself) and four lipoproteins called BamB-E. While the structure of the lipoproteins have been reported, the structure of full length BamA has been elusive. Recently though, we described the structure of BamA from two species of bacteria: Neisseria gonorrhoeae and Haemophilus ducreyi. BamA consists of a large periplasmic domain attached to a 16-strand transmembrane beta-barrel domain. Together, our crystal structures and molecule dynamics (MD) simulations revealed several structural features which gave clues to the mechanism by which BamA catalyzes beta-barrel assembly. The first is that the interior cavity is accessible in one BamA structure and conformationally closed in the other. Second, an exterior rim of the beta-barrel has a distinctly narrowed hydrophobic surface, locally destabilizing the outer membrane. Third, the beta-barrel can undergo lateral opening, suggesting a route from the interior cavity in BamA into the outer membrane. And fourth, a surface exposed exit pore positioned above the lateral opening site which may play a role in the biogenesis of extracellular loops. In this presentation, the crystal structures and MD simulations of BamA will be presented along with our work looking at the role of these four structural features in the role of BamA within the BAM complex.

scholarly journals PRED-TMBB2: improved topology prediction and detection of beta-barrel outer membrane proteins

2016 ◽  
Vol 32 (17) ◽  
pp. i665-i671 ◽  
Author(s):  
Konstantinos D. Tsirigos ◽  
Arne Elofsson ◽  
Pantelis G. Bagos
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Beta Barrel ◽  
Topology Prediction

scholarly journals Mechanisms of Resistance to the Contact-Dependent Bacteriocin CdzC/D inCaulobacter crescentus

2019 ◽  
Vol 201 (8) ◽  
Author(s):  
Leonor García-Bayona ◽  
Kevin Gozzi ◽  
Michael T. Laub
Keyword(s):  
Outer Membrane ◽  
Caulobacter Crescentus ◽  
Cell Envelope ◽  
Target Cells ◽  
Dependent Manner ◽  
Content Type ◽  
Repeat Protein ◽  
Outer Membranes ◽  
Oligotrophic Bacterium ◽  
Small Hydrophobic

ABSTRACTThe Cdz bacteriocin system allows the aquatic oligotrophic bacteriumCaulobacter crescentusto kill closely related species in a contact-dependent manner. The toxin, which aggregates on the surfaces of producer cells, is composed of two small hydrophobic proteins, CdzC and CdzD, each bearing an extended glycine-zipper motif, that together induce inner membrane depolarization and kill target cells. To further characterize the mechanism of Cdz delivery and toxicity, we screened for mutations that render a target strain resistant to Cdz-mediated killing. These mutations mapped to four loci, including a TonB-dependent receptor, a three-gene operon (namedzerRABforzipperenveloperesistance), andperA(forpentapeptideenveloperesistance). Mutations in thezerRABlocus led to its overproduction and to potential changes in cell envelope composition, which may diminish the susceptibility of cells to Cdz toxins. TheperAgene is also required to maintain a normal cell envelope, but our screen identified mutations that confer resistance to Cdz toxins without substantially affecting the cell envelope functions of PerA. We demonstrate that PerA, which encodes a pentapeptide repeat protein predicted to form a quadrilateral β-helix, localizes primarily to the outer membrane of cells, where it may serve as a receptor for the Cdz toxins. Collectively, these results provide new insights into the function and mechanisms of an atypical, contact-dependent bacteriocin system.IMPORTANCEBacteriocins are commonly used by bacteria to kill neighboring cells that compete for resources. Although most bacteriocins are secreted, the aquatic, oligotrophic bacteriumCaulobacter crescentusproduces a two-peptide bacteriocin, CdzC/D, that remains attached to the outer membranes of cells, enabling contact-dependent killing of cells lacking the immunity protein CdzI. The receptor for CdzC/D has not previously been reported. Here, we describe a genetic screen for mutations that confer resistance to CdzC/D. One locus identified,perA, encodes a pentapeptide repeat protein that resides in the outer membrane of target cells, where it may act as the direct receptor for CdzC/D. Collectively, our results provide new insight into bacteriocin function and diversity.

scholarly journals Gram-negative outer-membrane proteins with multiple β-barrel domains

2021 ◽  
Vol 118 (31) ◽  
pp. e2104059118
Author(s):  
Ron Solan ◽  
Joana Pereira ◽  
Andrei N. Lupas ◽  
Rachel Kolodny ◽  
Nir Ben-Tal
Keyword(s):  
Outer Membrane ◽  
De Novo ◽  
Outer Membrane Proteins ◽  
Gram Negative Bacteria ◽  
Single Chain ◽  
Gram Negative ◽  
Complementary Function ◽  
Beta Barrels ◽  
Β Sheets ◽  
The Individual

Outer-membrane beta barrels (OMBBs) are found in the outer membrane of gram-negative bacteria and eukaryotic organelles. OMBBs fold as antiparallel β-sheets that close onto themselves, forming pores that traverse the membrane. Currently known structures include only one barrel, of 8 to 36 strands, per chain. The lack of multi-OMBB chains is surprising, as most OMBBs form oligomers, and some function only in this state. Using a combination of sensitive sequence comparison methods and coevolutionary analysis tools, we identify many proteins combining multiple beta barrels within a single chain; combinations that include eight-stranded barrels prevail. These multibarrels seem to be the result of independent, lineage-specific fusion and amplification events. The absence of multibarrels that are universally conserved in bacteria with an outer membrane, coupled with their frequent de novo genesis, suggests that their functions are not essential but rather beneficial in specific environments. Adjacent barrels of complementary function within the same chain may allow for functions beyond those of the individual barrels.

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