PMID:16922505
| Citation |
Stegmeier, JF, Polleichtner, G, Brandes, N, Hotz, C and Andersen, C (2006) Importance of the adaptor (membrane fusion) protein hairpin domain for the functionality of multidrug efflux pumps. Biochemistry 45:10303-12 |
|---|---|
| Abstract |
Drug efflux pumps of Gram-negative bacteria are tripartite export machineries located in the bacterial envelopes contributing to multidrug resistance. Protein structures of all three components have been determined, but the exact interaction sites are still unknown. We could confirm that the hybrid system composed of Pseudomonas aeruginosa channel tunnel OprM and the Escherichia coli inner membrane complex, formed by adaptor protein (membrane fusion protein) AcrA and transporter AcrB of the resistance nodulation cell division (RND) family, is not functional. However, cross-linking experiments show that the hybrid exporter assembles. Exchange of the hairpin domain of AcrA with the corresponding hairpin from adaptor protein MexA of P. aeruginosa restored the functionality. This shows the importance of the MexA hairpin domain for the functional interaction with the OprM channel tunnel. On the basis of these results, we have modeled the interaction of the hairpin domain and the channel tunnel on a molecular level for AcrA and TolC as well as MexA and OprM, respectively. The model of two hairpin docking sites per TolC protomer corresponding with hexameric adaptor proteins was confirmed by disulfide cross-linking experiments. The role of this interaction for functional efflux pumps is discussed. |
| Links |
PubMed Online version:10.1021/bi060320g |
| Keywords |
Bacterial Outer Membrane Proteins/chemistry; Bacterial Outer Membrane Proteins/genetics; Drug Resistance, Multiple, Bacterial/genetics; Escherichia coli/chemistry; Escherichia coli/genetics; Membrane Transport Proteins/chemistry; Membrane Transport Proteins/genetics; Models, Molecular; Protein Structure, Tertiary; Pseudomonas aeruginosa/chemistry; Pseudomonas aeruginosa/genetics; Recombinant Fusion Proteins |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<annotationlinks/>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
References
See Help:References for how to manage references in EcoliWiki.