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TitleAssembly and channel opening of outer membrane protein in tripartite drug efflux pumps of Gram-negative bacteria.
Journal, issue, pagesJ Biol Chem, Vol. 287, Issue 15, Page 11740-11750, Year 2012
Publish dateApr 6, 2012
AuthorsYongbin Xu / Arne Moeller / So-Young Jun / Minho Le / Bo-Young Yoon / Jin-Sik Kim / Kangseok Lee / Nam-Chul Ha /
PubMed AbstractGram-negative bacteria are capable of expelling diverse xenobiotic substances from within the cell by use of three-component efflux pumps in which the energy-activated inner membrane transporter is ...Gram-negative bacteria are capable of expelling diverse xenobiotic substances from within the cell by use of three-component efflux pumps in which the energy-activated inner membrane transporter is connected to the outer membrane channel protein via the membrane fusion protein. In this work, we describe the crystal structure of the membrane fusion protein MexA from the Pseudomonas aeruginosa MexAB-OprM pump in the hexameric ring arrangement. Electron microscopy study on the chimeric complex of MexA and the outer membrane protein OprM reveals that MexA makes a tip-to-tip interaction with OprM, which suggests a docking model for MexA and OprM. This docking model agrees well with genetic results and depicts detailed interactions. Opening of the OprM channel is accompanied by the simultaneous exposure of a protein structure resembling a six-bladed cogwheel, which intermeshes with the complementary cogwheel structure in the MexA hexamer. Taken together, we suggest an assembly and channel opening model for the MexAB-OprM pump. This study provides a better understanding of multidrug resistance in Gram-negative bacteria.
External linksJ Biol Chem / PubMed:22308040 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution3.499 - 24.0 Å
Structure data

EMDB-2044:
Electron microscopy of Aa MacA-MexA alpha;-hybrid and Aa MacA-OprM alpha;-hybrid- dimer
Method: EM (single particle) / Resolution: 24.0 Å

PDB-4dk0:
Crystal structure of MacA from Actinobacillus actinomycetemcomitans
Method: X-RAY DIFFRACTION / Resolution: 3.5 Å

PDB-4dk1:
Crystal Structure of MacA-MexA chimeric protein, containing the Pseudomonas aeruginosa MexA alpha-hairpin domain.
Method: X-RAY DIFFRACTION / Resolution: 3.499 Å

Source
  • Escherichia coli (E. coli)
  • aggregatibacter actinomycetemcomitans (bacteria)
  • pseudomonas aeruginosa (bacteria)
KeywordsMEMBRANE PROTEIN / alpha-hairpin / lipoyl / beta-barrel / PERIPLASMIC PROTEIN / beta-barrel domains

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