title: Alternative folding pathways of the major porin OprF of Pseudomonas aeruginosa.
abstract: OprF is the major porin of Pseudomonas aeruginosa and allows very slow, nonspecific, diffusion of solutes. The low permeability of this porin channel is a major factor that enhances other types of resistance mechanisms and often creates strong multidrug resistance in this nosocomial pathogen. We have previously shown that the low permeability is caused by the folding of OprF into two conformers: a majority, two-domain closed-channel conformer containing the N-terminal transmembrane β-barrel and the C-terminal periplasmic, globular domain; and a minority, one-domain open-channel conformer comprising < 5% of the protein population. Our analysis of the bifurcate folding pathway using site-directed mutagenesis showed that slowing down the folding of the two-domain conformer increases the fraction of the open, one-domain conformer. Use of outer membrane protein assembly machinery mutants showed that the absence of the Skp chaperone led to an increased proportion of open conformers. As many environmental pathogens causing nosocomial infections appear to have outer membrane protein (OmpA)/OprF homologs as the major porin, efforts to understand the low permeability of these 'slow porins' are important in our fight against these organisms.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Sugawara
authors.forename: Keiji
authors.initials: K
authors.lastname: Nagano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nikaido
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D018272:Porins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D011550:Pseudomonas aeruginosa / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D018832:Molecular Chaperones; C547605:OprF protein, Pseudomonas aeruginosa; D018272:Porins