Structure and function of Neisseria gonorrhoeae MtrF illuminates a class of antimetabolite efflux pumps.

Structure and function of Neisseria gonorrhoeae MtrF illuminates a class of antimetabolite efflux pumps.
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DOI:
10.1016/j.celrep.2015.03.003
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发表时间:
2015-04-07
期刊:
影响因子:
8.8
通讯作者:
Yu EW
Yu EW
中科院分区:
生物学1区
文献类型:
--
作者:
Su CC;Bolla JR;Kumar N;Radhakrishnan A;Long F;Delmar JA;Chou TH;Rajashankar KR;Shafer WM;Yu EW

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淋病奈瑟菌是一种专性人类病原体,也是性传播疾病淋病的病原体。由于抗药性菌株感染的比例不断增加,这种疾病的控制受到损害,这种菌株正在以惊人的速度增长。N.淋病MtrF是一种完整的膜蛋白,属于AbgT转运蛋白家族,其结构信息不可用。在这里,我们描述的晶体结构的MtrF,揭示了一个二聚体分子的架构不同于所有其他家庭的转运。MtrF是一种碗状二聚体,具有从细胞质延伸到膜双层一半的充满溶剂的盆。转运蛋白的每个亚基含有9个跨膜螺旋和2个发夹,构成了一个合理的底物转运途径。晶体结构和生化功能分析的组合表明,MtrF是抗生素外排泵,介导细菌对磺胺类抗代谢药物的耐药性。
Neisseria gonorrhoeae is an obligate human pathogen and the causative agent of the sexually-transmitted disease gonorrhea. The control of this disease has been compromised by the increasing proportion of infections due to antibiotic-resistant strains, which are growing at an alarming rate. N. gonorrhoeae MtrF is an integral membrane protein, which belongs to the AbgT family of transporters for which no structural information is available. Here we describe the crystal structure of MtrF, revealing a dimeric molecule with architecture distinct from all other families of transporters. MtrF is a bowl-shaped dimer with a solvent-filled basin extending from the cytoplasm to halfway across the membrane bilayer. Each subunit of the transporter contains nine transmembrane helices and two hairpins, posing a plausible pathway for substrate transport. A combination of the crystal structure and biochemical functional assays suggests that MtrF is an antibiotic efflux pump, mediating bacterial resistance to sulfonamide antimetabolite drugs.
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