3FPP

Crystal structure of E.coli MacA

Summary for 3FPP

• Entry DOI: 10.2210/pdb3fpp/pdb
• Descriptor: Macrolide-specific efflux protein macA (1 entity in total)
• Functional Keywords: hexameric assembly, membrane fusion protein, drug efflux pump, periplasmic protein, antibiotic resistance, cell inner membrane, cell membrane, membrane, transport, membrane protein
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane; Peripheral membrane protein: P75830
• Total number of polymer chains: 2
• Total formula weight: 74374.48

Authors

Yum, S.,Xu, Y.,Piao, S.,Ha, N.-C. (deposition date: 2009-01-06, release date: 2009-04-28, Last modification date: 2024-04-03)

Primary citation

Yum, S.,Xu, Y.,Piao, S.,Sim, S.-H.,Kim, H.-M.,Jo, W.-S.,Kim, K.-J.,Kweon, H.-S.,Jeong, M.-H.,Jeon, H.,Lee, K.,Ha, N.-C.
Crystal structure of the periplasmic component of a tripartite macrolide-specific efflux pump
J.Mol.Biol., 387:1286-1297, 2009

PubMed Abstract: In Gram-negative bacteria, type I protein secretion systems and tripartite drug efflux pumps have a periplasmic membrane fusion protein (MFP) as an essential component. MFPs bridge the outer membrane factor and an inner membrane transporter, although the oligomeric state of MFPs remains unclear. The most characterized MFP AcrA connects the outer membrane factor TolC and the resistance-nodulation-division-type efflux transporter AcrB, which is a major multidrug efflux pump in Escherichia coli. MacA is the periplasmic MFP in the MacAB-TolC pump, where MacB was characterized as a macrolide-specific ATP-binding-cassette-type efflux transporter. Here, we report the crystal structure of E. coli MacA and the experimentally phased map of Actinobacillus actinomycetemcomitans MacA, which reveal a domain orientation of MacA different from that of AcrA. Notably, a hexameric assembly of MacA was found in both crystals, exhibiting a funnel-like structure with a central channel and a conical mouth. The hexameric MacA assembly was further confirmed by electron microscopy and functional studies in vitro and in vivo. The hexameric structure of MacA provides insight into the oligomeric state in the functional complex of the drug efflux pump and type I secretion system.

PubMed: 19254725
DOI: 10.1016/j.jmb.2009.02.048

Experimental method

X-RAY DIFFRACTION (2.99 Å)