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

J Mol Biol. 2015 Jul 17;427(14):2329-39. doi: 10.1016/j.jmb.2015.03.016. Epub 2015 Apr 3.


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.

Keywords: Acinetobacter baumannii; antibiotic resistance; crystal structure; outer membrane protein; small molecule uptake.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinetobacter baumannii / metabolism*
  • Amino Acids / metabolism*
  • Anti-Bacterial Agents / metabolism
  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / metabolism*
  • Biological Transport
  • Carbapenems / metabolism
  • Crystallography, X-Ray
  • Glycine / metabolism
  • Ion Channels / chemistry
  • Ion Channels / metabolism
  • Membrane Transport Proteins / chemistry
  • Membrane Transport Proteins / metabolism
  • Models, Molecular
  • Ornithine / metabolism
  • Porins / chemistry*
  • Porins / metabolism*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary


  • Amino Acids
  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • CarO protein, Acinetobacter baumannii
  • Carbapenems
  • Ion Channels
  • Membrane Transport Proteins
  • Porins
  • Ornithine
  • Glycine

Associated data

  • PDB/4FUV
  • PDB/4RL9
  • PDB/4RLB
  • PDB/4RLC