Structure and Function of Neisseria gonorrhoeae MtrF Illuminates a Class of Antimetabolite Efflux Pumps

• Type of Material: Article
• Authors: Chih-Chia Su, Iowa State University; Jani Reddy Bolla, Iowa State University; Nitin Kumar, Iowa State University; Abhijith Radhakrishnan, Iowa State University; Feng Long, Iowa State University; Jared A. Delmar, Iowa State University; Tsung-Han Chou, Iowa State University; Kanagalaghatta R. Rajashankar, Cornell University; William Shafer, Emory University; Edward W. Yu, Iowa State University
• Language: English
• Date: 2015-04-07
• Publisher: Elsevier (Cell Press): OAJ
• Publication Version: Final Published Version
• Copyright Statement: © 2015 The Authors. Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.celrep.2015.03.003
• Title of Journal or Parent Work: Cell Reports
• ISSN: 2211-1247
• Volume: 11
• Issue: 1
• Start Page: 61
• End Page: 70
• Grant/Funding Information: Use of the Advanced Photon Source is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357.; This work was supported by NIH Grants R37AI021150 (W.M.S.) and R01GM086431 (E.W.Y.) and a VA Merit Award (W.M.S.) from the Medical Research Service of the Department of Veterans Affairs.; This work is based upon research conducted at the Northeastern Collaborative Access Team beamlines of the Advanced Photon Source, supported by an award GM103403 from the National Institutes of General Medical Sciences.
• Keywords: P-AMINOBENZOYL-GLUTAMATE; ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE; Science & Technology; HYDROPHOBIC AGENTS; TRANSPORTER; PROTEIN; CRYSTAL-STRUCTURES; SOFTWARE; FAMILY; Cell Biology; SYSTEM; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

Abstract

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.