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

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 that 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.
Authors:
 [1] ;  [2] ;  [3] ;  [4] ;  [5] ;  [5] ;  [5] ;  [6] ;  [7] ;  [8]
  1. Iowa State Univ., Ames, IA (United States) Dept. of Physics and Astronomy; Emory Univ., Atlanta, GA (United States)
  2. Iowa State Univ., Ames, IA (United States) Dept. of Chemistry; Emory Univ., Atlanta, GA (United States)
  3. Iowa State Univ., Ames, IA (United States) Dept. of Chemistry.
  4. Iowa State Univ., Ames, IA (United States) Dept. of Chemistry,
  5. Iowa State Univ., Ames, IA (United States) Dept. of Physics and Astronomy.
  6. Argonne National Lab. (ANL), Argonne, IL (United States)
  7. Emory Univ. School of Medicine, Atlanta, GA (United States). Dept. of Microbiology and Immunology; VA Medical Center, Decatur, GA (United States); Emory Univ. School of Medicine, Atlanta, GA (United States). Emory Antibiotic Resistance Center.
  8. Iowa State Univ., Ames, IA (United States) Dept. of Physics and Astronomy; Iowa State Univ., Ames, IA (United States) Dept. of Chemistry.
Publication Date:
OSTI Identifier:
1243355
Grant/Contract Number:
AC02-06CH11357
Type:
Published Article
Journal Name:
Cell Reports
Additional Journal Information:
Journal Volume: 11; Journal Issue: 1; Journal ID: ISSN 2211-1247
Publisher:
Elsevier
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org:
National Institutes of Health (NIH); Department of Veterans Affairs; USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES