2DRD

Crystal structure of a multidrug transporter reveal a functionally rotating mechanism

Summary for 2DRD

• Entry DOI: 10.2210/pdb2drd/pdb
• Related: 2DHH 2DR6
• Descriptor: ACRB, (4S,4AS,5AR,12AS)-4,7-BIS(DIMETHYLAMINO)-3,10,12,12A-TETRAHYDROXY-1,11-DIOXO-1,4,4A,5,5A,6,11,12A-OCTAHYDROTETRACENE-2- CARBOXAMIDE (2 entities in total)
• Functional Keywords: membrane transporter, membrane protein, multidrug efflux, drug resistance, transporter, exporter, antiporter
• Biological source: Escherichia coli
• Cellular location: Cell inner membrane; Multi-pass membrane protein: P31224
• Total number of polymer chains: 3
• Total formula weight: 343110.70

Authors

Murakami, S.,Nakashima, R.,Yamashita, E.,Matsumoto, T. (deposition date: 2006-06-08, release date: 2006-08-22, Last modification date: 2024-03-13)

Primary citation

Murakami, S.,Nakashima, R.,Yamashita, E.,Matsumoto, T.,Yamaguchi, A.
Crystal structures of a multidrug transporter reveal a functionally rotating mechanism
Nature, 443:173-179, 2006

PubMed Abstract: AcrB is a principal multidrug efflux transporter in Escherichia coli that cooperates with an outer-membrane channel, TolC, and a membrane-fusion protein, AcrA. Here we describe crystal structures of AcrB with and without substrates. The AcrB-drug complex consists of three protomers, each of which has a different conformation corresponding to one of the three functional states of the transport cycle. Bound substrate was found in the periplasmic domain of one of the three protomers. The voluminous binding pocket is aromatic and allows multi-site binding. The structures indicate that drugs are exported by a three-step functionally rotating mechanism in which substrates undergo ordered binding change.

PubMed: 16915237
DOI: 10.1038/nature05076

Experimental method

X-RAY DIFFRACTION (3.1 Å)