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Mol Cell ; 81(9): 2000-2012.e3, 2021 05 06.
Article in English | MEDLINE | ID: mdl-33705710

ABSTRACT

The ß-barrel assembly machine (BAM) integrates ß-barrel proteins into the outer membrane (OM) of Gram-negative bacteria. An essential BAM subunit (BamA) catalyzes integration by promoting the formation of a hybrid-barrel intermediate state between its own ß-barrel domain and that of its client proteins. Here we show that in addition to catalyzing the integration of ß-barrel proteins, BamA functions as a polypeptide export channel. In vivo structural mapping via intermolecular disulfide crosslinking showed that the extracellular "passenger" domain of a member of the "autotransporter" superfamily of virulence factors traverses the OM through the BamA ß-barrel lumen. Furthermore, we demonstrate that a highly conserved residue within autotransporter ß-barrels is required to position the passenger inside BamA to initiate translocation and that during translocation, the passenger stabilizes the hybrid-barrel state. Our results not only establish a new function for BamA but also unify the divergent functions of BamA and other "Omp85" superfamily transporters.


Subject(s)
Bacterial Outer Membrane Proteins/metabolism , Bacterial Outer Membrane/metabolism , Escherichia coli K12/metabolism , Escherichia coli Proteins/metabolism , Bacterial Outer Membrane Proteins/genetics , Biological Transport , Conserved Sequence , Escherichia coli K12/genetics , Escherichia coli Proteins/genetics , Protein Conformation , Protein Folding , Structure-Activity Relationship , Tryptophan
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