Lateral Opening and Exit Pore Formation Are Required for BamA Function

Noinaj, Nicholas; Kuszak, Adam; Balusek, Curtis; Gumbart, James C.; Buchanan, Susan K.

doi:10.1016/j.str.2014.05.008

Cited by 178 publications

(292 citation statements)

References 48 publications

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“…This model indeed concurs with mechanisms proposed for BamA and TamA based on recent X-ray structures 11,12,34 . A lateral opening of the Omp85 b-barrel to enable the transfer of the substrate into the lipid bilayer has been proposed, and evidence supporting such a mechanism was recently obtained 43 . A lateral opening implies that the soluble, surface loop regions of the substrate proteins transit through the barrel while the transmembrane segments are integrated in the bilayer, as discussed in ref.…”

Section: Discussionmentioning

confidence: 95%

Translocation path of a substrate protein through its Omp85 transporter

et al. 2014

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TpsB proteins are Omp85 superfamily members that mediate protein translocation across the outer membrane of Gram-negative bacteria. Omp85 transporters are composed of N-terminal POTRA domains and a C-terminal transmembrane b-barrel. In this work, we track the in vivo secretion path of the Bordetella pertussis filamentous haemagglutinin (FHA), the substrate of the model TpsB transporter FhaC, using site-specific crosslinking. The conserved secretion domain of FHA interacts with the POTRA domains, specific extracellular loops and strands of FhaC and the inner b-barrel surface. The interaction map indicates a funnel-like pathway, with conformationally flexible FHA entering the channel in a non-exclusive manner and exiting along a four-stranded b-sheet at the surface of the FhaC barrel. This sheet of FhaC guides the secretion domain of FHA along discrete steps of translocation and folding. This work demonstrates that the Omp85 barrel serves as a channel for translocation of substrate proteins.

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Section: Discussionmentioning

confidence: 95%

Translocation path of a substrate protein through its Omp85 transporter

et al. 2014

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“…If and how the BAM complex is also important for hairpin formation is unclear. Recent structural and functional data on the BAM complex suggest that a hybrid barrel is formed between the BamA barrel and the substrate (45)(46)(47)(48). From this intermediate, the substrate barrel is then released in a process that can be described as "budding."…”

Section: Discussionmentioning

confidence: 99%

The Inverse Autotransporter Intimin Exports Its Passenger Domain via a Hairpin Intermediate

Oberhettinger

Leo

Linke

et al. 2015

Journal of Biological Chemistry

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Background:Intimin exports its C-terminal passenger domain through an N-terminal ␤-barrel onto the bacterial surface. Results: Insertion of an epitope tag at the very N terminus of the passenger domain stalls the export of the passenger. Conclusion:The intimin passenger adopts a hairpin conformation during translocation. Significance: Our results confirm the hairpin model of inverse autotransport where the passenger is translocated from the N to the C terminus.

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“…The mechanistic details for how the BAM complex catalyzes uOMP folding are not well understood (20,(39)(40)(41)(42)(43)(44). Even lacking this information, we can use OMPBioM to estimate the effective rate necessary for BAM-assisted OMP folding.…”

Section: The Folding Rate Enhancement Provided By Sura Is Necessary Butmentioning

confidence: 99%

Dynamic periplasmic chaperone reservoir facilitates biogenesis of outer membrane proteins

Costello

Plummer

Fleming

2016

Proc. Natl. Acad. Sci. U.S.A.

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Outer membrane protein (OMP) biogenesis is critical to bacterial physiology because the cellular envelope is vital to bacterial pathogenesis and antibiotic resistance. The process of OMP biogenesis has been studied in vivo, and each of its components has been studied in isolation in vitro. This work integrates parameters and observations from both in vivo and in vitro experiments into a holistic computational model termed "Outer Membrane Protein Biogenesis Model" (OMPBioM). We use OMPBioM to assess OMP biogenesis mathematically in a global manner. Using deterministic and stochastic methods, we are able to simulate OMP biogenesis under varying genetic conditions, each of which successfully replicates experimental observations. We observe that OMPs have a prolonged lifetime in the periplasm where an unfolded OMP makes, on average, hundreds of short-lived interactions with chaperones before folding into its native state. We find that some periplasmic chaperones function primarily as quality-control factors; this function complements the folding catalysis function of other chaperones. Additionally, the effective rate for the β-barrel assembly machinery complex necessary for physiological folding was found to be higher than has currently been observed in vitro. Overall, we find a finely tuned balance between thermodynamic and kinetic parameters maximizes OMP folding flux and minimizes aggregation and unnecessary degradation. In sum, OMPBioM provides a global view of OMP biogenesis that yields unique insights into this essential pathway.T he cellular envelope of Gram-negative bacteria is comprised of two membranes separated by an aqueous compartment termed the "periplasm." The outer membrane of the cellular envelope contains integral β-barrel membrane proteins referred to as "outer membrane proteins" (OMPs) (1, 2). The outer membrane and OMPs provide the first barrier between bacteria and the environment and are essential to many important cellular processes including metabolic transport, bacterial virulence, and antibiotic resistance (3-5). Understanding the pathway by which OMPs traverse the periplasm and attain their native functional state is essential to an ability to manipulate this element of the bacterial cell.The OMP biogenesis process is distinct from the folding of cytosolic proteins because it involves a unique collection of obstacles. First, OMPs do not adopt their folded conformations while in an aqueous environment (6). Rather, unfolded OMPs (uOMPs) must be transported across the periplasm to reach their native membrane. Because of their marginal solubility in water, this process must be tightly controlled to avoid aggregation. Second, structures of folded OMPs (fOMPs) show that these proteins contain water-solvated residues in loops on the outer surfaces of bacteria. The desolvation and transport of these polar and ionizable side chains across the outer membrane represent significant kinetic barriers to OMP folding (7). Third, Gram-negative bacteria maintain a high density of fOMP in the expanding oute...

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Lateral Opening and Exit Pore Formation Are Required for BamA Function

Cited by 178 publications

References 48 publications

Translocation path of a substrate protein through its Omp85 transporter

Translocation path of a substrate protein through its Omp85 transporter

The Inverse Autotransporter Intimin Exports Its Passenger Domain via a Hairpin Intermediate

Dynamic periplasmic chaperone reservoir facilitates biogenesis of outer membrane proteins

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