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
中科院分区:
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
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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