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Small-Molecule Transport by CarO, an Abundant Eight-Stranded β-Barrel Outer Membrane Protein from Acinetobacter baumannii

DOI: 10.1016/j.jmb.2015.03.016 DOI Help
PMID: 25846137 PMID Help

Authors: Michael Zahn (Newcastle University) , Tommaso D'agostino (University of Cagliari) , Elif Eren (National Institutes of Health, Bethesda) , Arnaud Baslé (Newcastle University) , Matteo Ceccarelli (University of Cagliari) , Bert Van Den Berg (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Molecular Biology , VOL 427 (14) , PAGES 2329 - 2339

State: Published (Approved)
Published: July 2015

Abstract: Outer membrane (OM) β-barrel proteins composed of 12–18 β-strands mediate cellular entry of small molecules in Gram-negative bacteria. Small OM proteins with barrels of 10 strands or less are not known to transport small molecules. CarO (carbapenem-associated outer membrane protein) from Acinetobacter baumannii is a small OM protein that has been implicated in the uptake of ornithine and carbapenem antibiotics. Here we report crystal structures of three isoforms of CarO. The structures are very similar and show a monomeric eight-stranded barrel lacking an open channel. CarO has a substantial extracellular domain resembling a glove that contains all the divergent residues between the different isoforms. Liposome swelling experiments demonstrate that full-length CarO and a “loop-less” truncation mutant mediate small-molecule uptake at low levels but that they are unlikely to mediate passage of carbapenem antibiotics. These results are confirmed by biased molecular dynamics simulations that allowed us to quantitatively model the transport of selected small molecules.

Journal Keywords: Acinetobacter Baumannii; Outer Membrane Protein; Crystal Structure; Small Molecule Uptake; Antibiotic Resistance

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-Macromolecular Crystallography

Other Facilities: National Synchrotron Light Source