Crystal structures of a multidrug transporter reveal a functionally rotating mechanism

• Published in: Nature Vol. 443; no. 7108; pp. 173 - 179
• Main Authors: Murakami, Satoshi, Nakashima, Ryosuke, Yamashita, Eiki, Matsumoto, Takashi, Yamaguchi, Akihito
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 14.09.2006; Nature Publishing Group
• Subjects: Bacterial Outer Membrane Proteins - metabolism; Binding Sites; Biological and medical sciences; Cell Membrane - metabolism; Crystal structure; Crystalline structure; Crystallography, X-Ray; E coli; Escherichia coli; Escherichia coli - chemistry; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Lipoproteins - metabolism; Membrane Transport Proteins; Membranes; Minocycline - chemistry; Minocycline - metabolism; Models, Biological; Models, Molecular; Molecular biophysics; Multidrug Resistance-Associated Proteins - chemistry; Multidrug Resistance-Associated Proteins - metabolism; Protein Structure, Secondary; Protein Structure, Tertiary; Proteins; Rotation; Structure in molecular biology; Structure-Activity Relationship; Substrate Specificity; Substrates; Bacteria; Membrane transport; Escherichia coli; Mechanism; Enterobacteriaceae; Crystalline structure
• ISSN: 0028-0836; 1476-4687; 1476-4687; 1476-4679
• DOI: 10.1038/nature05076

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.