Substrate-bound and substrate-free outward-facing structures of a multidrug ABC exporter

被引：25

作者：

Chaptal, Vincent ^{[1
]}

Zampieri, Veronica ^{[1
,9
]}

Wiseman, Benjamin ^{[1
,2
,10
]}

Orelle, Cedric ^{[3
]}

Martin, Juliette ^{[4
]}

Nguyen, Kim-Anh ^{[5
]}

Gobet, Alexia ^{[1
]}

Di Cesare, Margot ^{[3
]}

Magnard, Sandrine ^{[1
]}

Javed, Waqas ^{[3
,8
]}

Eid, Jad ^{[1
]}

Kilburg, Arnaud ^{[1
]}

Peuchmaur, Marine ^{[6
]}

Marcoux, Julien ^{[7
]}

Monticelli, Luca ^{[4
]}

Hogbom, Martin ^{[2
]}

Schoehn, Guy ^{[8
]}

Jault, Jean-Michel ^{[3
]}

Boumendjel, Ahcene ^{[5
]}

Falson, Pierre ^{[1
]}

机构：

[1] Univ Lyon, Drug Resistance & Membrane Prot Grp, Mol Microbiol & Struct Biochem Lab, CNRS UMR 5086,IBCP, 7 Passage Vercors, F-69367 Lyon, France

[2] Stockholm Univ, Dept Biochem & Biophys, Arrhenius Labs Nat Sci, Stockholm, Sweden

[3] Univ Lyon, Bacterial Nucleotide Binding Prot Grp, Mol Microbiol & Struct Biochem Lab, CNRS UMR 5086,IBCP, 7 Passage Vercors, F-69367 Lyon, France

[4] Univ Lyon, Modeling Biol Macromol Grp, Mol Microbiol & Struct Biochem Lab, CNRS UMR 5086,IBCP, 7 Passage Vercors, F-69367 Lyon, France

[5] Univ Grenoble Alpes, LRB, INSERM, F-38000 Grenoble, France

[6] Univ Grenoble Alpes, CNRS, DPM UMR 5063, F-38041 Grenoble, France

[7] Univ Toulouse, Inst Pharmacol & Biol Struct IPBS, UPS, CNRS,UMR 5089, F-31000 Toulouse, France

[8] Univ Grenoble Alpes, IBS, CNRS, CEA, F-38000 Grenoble, France

[9] European Mol Biol Lab, 71 Ave Martyrs,CS 90181, F-38042 Grenoble 9, France

[10] Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 04期

基金：

瑞典研究理事会;

关键词：

BINDING CASSETTE TRANSPORTER; ATP-BINDING; P-GLYCOPROTEIN; BACILLUS-SUBTILIS; MOLECULAR-BASIS; RESISTANCE; FLEXIBILITY; DYNAMICS; MSBA; PRINCIPLES;

D O I：

10.1126/sciadv.abg9215

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：

Multidrug ABC transporters translocate drugs across membranes by a mechanism for which the molecular features of drug release are so far unknown. Here, we resolved three ATP-Mg2+-bound outward-facing conformations of the Bacillus subtilis (homodimeric) BmrA by x-ray crystallography and single-particle cryo-electron microscopy (EM) in detergent solution, one of them with rhodamine 6G (R6G), a substrate exported by BmrA when over-expressed in B. subtilis. Two R6G molecules bind to the drug-binding cavity at the level of the outer leaflet, between transmembrane (TM) helices 1-2 of one monomer and TM5'-6' of the other. They induce a rearrangement of TM1-2, highlighting a local flexibility that we confirmed by hydrogen/deuterium exchange and molecular dynamics simulations. In the absence of R6G, simulations show a fast postrelease occlusion of the cavity driven by hydrophobicity, while when present, R6G can move within the cavity, maintaining it open.

引用

页数：10

共 50 条

[41] Enhanced Faraday rotation by a Fano resonance in substrate-free three-dimensional magnetoplasmonic structures
Cheng, Tong-Huai
Yang, Weihao
Liu, Zhaochao
Feng, Hua Yu
Qin, Jun
Ma, Yifei
Li, Shicheng
Bi, Lei
Luo, Feng
NANOSCALE, 2023, 15 (38) : 15583 - 15589
[42] Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site
Weixiao Y. Wahlgren
Elin Dunevall
Rachel A. North
Aviv Paz
Mariafrancesca Scalise
Paola Bisignano
Johan Bengtsson-Palme
Parveen Goyal
Elin Claesson
Rhawnie Caing-Carlsson
Rebecka Andersson
Konstantinos Beis
Ulf J. Nilsson
Anne Farewell
Lorena Pochini
Cesare Indiveri
Michael Grabe
Renwick C. J. Dobson
Jeff Abramson
S. Ramaswamy
Rosmarie Friemann
Nature Communications, 9
[43] Structures of the Neisseria meningitides methionine-binding protein MetQ in substrate-free form and bound to l- and d-methionine isomers
Nguyen, Phong T.
Lai, Jeffrey Y.
Kaiser, Jens T.
Rees, Douglas C.
PROTEIN SCIENCE, 2019, 28 (10) : 1750 - 1757
[44] A MEMS thermal shear stress sensor produced by a combination of substrate-free structures with anodic bonding technology
Ou, Yi
Qu, Furong
Wang, Guanya
Nie, Mengyan
Li, Zhigang
Ou, Wen
Xie, Changqing
APPLIED PHYSICS LETTERS, 2016, 109 (02)
[45] Induced fit in guanidino kinases - comparison of substrate-free and transition state analog structures of arginine kinase
Yousef, MS
Clark, SA
Pruett, PK
Somasundaram, T
Ellington, WR
Chapman, M
PROTEIN SCIENCE, 2003, 12 (01) : 103 - 111
[46] Crystal Structure Analysis of Free and Substrate-Bound 6-Hydroxy-L-Nicotine Oxidase from Arthrobacter nicotinovorans
Kachalova, Galina S.
Bourenkov, Gleb P.
Mengesdorf, Thorsten
Schenk, Susann
Maun, Henry R.
Burghammer, Manfred
Riekel, Christian
Decker, Karl
Bartunik, Hans D.
JOURNAL OF MOLECULAR BIOLOGY, 2010, 396 (03) : 785 - 799
[47] Crystal Structures of the Substrate-Bound Forms of Red Chlorophyll Catabolite Reductase: Implications for Site-Specific and Stereospecific Reaction
Sugishima, Masakazu
Okamoto, Yukihiro
Noguchi, Masato
Kohchi, Takayuki
Tamiaki, Hitoshi
Fukuyama, Keiichi
JOURNAL OF MOLECULAR BIOLOGY, 2010, 402 (05) : 879 - 891
[48] Relation between the Catalytic Efficiency of the Synthetic Analogues of Catechol Oxidase with Their Electrochemical Property in the Free State and Substrate-Bound State
Chakraborty, Prateeti
Adhikary, Jaydeep
Ghosh, Bipinbihari
Sanyal, Ria
Chattopadhyay, Shyamal Kumar
Bauza, Antonio
Frontera, Antonio
Zangrando, Ennio
Das, Debasis
INORGANIC CHEMISTRY, 2014, 53 (16) : 8257 - 8269
[49] Structures of the Substrate-free and Product-bound Forms of HmuO, a Heme Oxygenase from Corynebacterium diphtheriae X-RAY CRYSTALLOGRAPHY AND MOLECULAR DYNAMICS INVESTIGATION
Unno, Masaki
Ardevol, Albert
Rovira, Carme
Ikeda-Saito, Masao
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (48) : 34443 - 34458
[50] Crystal Structures of Substrate-Free and Nitrosyl Cytochrome P450cin: Implications for O2 Activation
Madrona, Yarrow
Tripathi, Sarvind
Li, Huiying
Poulos, Thomas L.
BIOCHEMISTRY, 2012, 51 (33) : 6623 - 6631

← 1 2 3 4 5 →