Structure and Function of Neisseria gonorrhoeae MtrF Illuminates a Class of Antimetabolite Efflux Pumps
Chih-Chia Su,
Jani Reddy Bolla,
Nitin Kumar,
Abhijith Radhakrishnan,
Feng Long,
Jared A. Delmar,
Tsung-Han Chou,
Kanagalaghatta R. Rajashankar,
William M. Shafer,
Edward W. Yu
Affiliations
Chih-Chia Su
Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA
Jani Reddy Bolla
Department of Chemistry, Iowa State University, Ames, IA 50011, USA
Nitin Kumar
Department of Chemistry, Iowa State University, Ames, IA 50011, USA
Abhijith Radhakrishnan
Department of Chemistry, Iowa State University, Ames, IA 50011, USA
Feng Long
Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA
Jared A. Delmar
Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA
Tsung-Han Chou
Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA
Kanagalaghatta R. Rajashankar
NE-CAT and Department of Chemistry and Chemical Biology, Cornell University, Building 436E, Argonne National Laboratory, 9700 S. Cass Avenue, Argonne, IL 60439, USA
William M. Shafer
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
Edward W. Yu
Department of Physics and Astronomy, Iowa State University, Ames, IA 50011, USA
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.
