Crystal structures of a multidrug transporter reveal a functionally rotating mechanism

被引：567

作者：

Murakami, Satoshi ^{[1
]}

Nakashima, Ryosuke

Yamashita, Eiki

Matsumoto, Takashi

Yamaguchi, Akihito

机构：

[1] Osaka Univ, Inst Sci & Ind Res, Dept Cell Membrane Biol, Osaka 5670047, Japan

[2] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan

[3] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan

[4] Osaka Univ, Inst Prot Res, Suita, Osaka 5650871, Japan

[5] Osaka Univ, Fac Pharmaceut Sci, Suita, Osaka 5650871, Japan

[6] SOSHO Inc, Osaka 5410053, Japan

来源：

NATURE | 2006年 / 443卷 / 7108期

基金：

日本科学技术振兴机构;

关键词：

D O I：

10.1038/nature05076

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：173 / 179

页数：7

共 43 条

[11] Structure of the periplasmic component of a bacterial drug efflux pump [J].

Higgins, MK ;

Bokma, E ;

Koronakis, E ;

Hughes, C ;

Koronakis, V .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (27) :9994-9999

[12] IMPROVED METHODS FOR BUILDING PROTEIN MODELS IN ELECTRON-DENSITY MAPS AND THE LOCATION OF ERRORS IN THESE MODELS [J].

JONES, TA ;

ZOU, JY ;

COWAN, SW ;

KJELDGAARD, M .

ACTA CRYSTALLOGRAPHICA SECTION A, 1991, 47 :110-119

[13] Software for handling macromolecular envelopes [J].

Kleywegt, GJ ;

Jones, TA .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1999, 55 :941-944

[14] DETECTION, DELINEATION, MEASUREMENT AND DISPLAY OF CAVITIES IN MACROMOLECULAR STRUCTURES [J].

KLEYWEGT, GJ ;

JONES, TA .

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :178-185

[15] Crystal structure of the bacterial membrane protein TolC central to multidrug efflux and protein export [J].

Koronakis, V ;

Sharff, A ;

Koronakis, E ;

Luisi, B ;

Hughes, C .

NATURE, 2000, 405 (6789) :914-919

[16] MOLSCRIPT - A PROGRAM TO PRODUCE BOTH DETAILED AND SCHEMATIC PLOTS OF PROTEIN STRUCTURES [J].

KRAULIS, PJ .

JOURNAL OF APPLIED CRYSTALLOGRAPHY, 1991, 24 :946-950

[17] Efflux-mediated drug resistance in bacteria [J].

Li, XZ ;

Nikaido, H .

DRUGS, 2004, 64 (02) :159-204

[18] MOLECULAR-CLONING AND CHARACTERIZATION OF ACRA AND ACRE GENES OF ESCHERICHIA-COLI [J].

MA, D ;

COOK, DN ;

ALBERTI, M ;

PON, NG ;

NIKAIDO, H ;

HEARST, JE .

JOURNAL OF BACTERIOLOGY, 1993, 175 (19) :6299-6313

[19] GENES ACRA AND ACRB ENCODE A STRESS-INDUCED EFFLUX SYSTEM OF ESCHERICHIA-COLI [J].

MA, D ;

COOK, DN ;

ALBERTI, M ;

PON, NG ;

NIKAIDO, H ;

HEARST, JE .

MOLECULAR MICROBIOLOGY, 1995, 16 (01) :45-55

[20] On the mechanism of substrate specificity by resistance nodulation division (RND)-type multidrug resistance pumps:: the large periplasmic loops of MexD from Pseudomonas aeruginosa are involved in substrate recognition [J].

Mao, WM ;

Warren, MS ;

Black, DS ;

Satou, T ;

Murata, T ;

Nishino, T ;

Gotoh, N ;

Lomovskaya, O .

MOLECULAR MICROBIOLOGY, 2002, 46 (03) :889-901

← 1 2 3 4 5 →