title: Substrate specificity within a family of outer membrane carboxylate channels.
abstract: Many Gram-negative bacteria, including human pathogens such as Pseudomonas aeruginosa, do not have large-channel porins. This results in an outer membrane (OM) that is highly impermeable to small polar molecules, making the bacteria intrinsically resistant towards many antibiotics. In such microorganisms, the majority of small molecules are taken up by members of the OprD outer membrane protein family. Here we show that OprD channels require a carboxyl group in the substrate for efficient transport, and based on this we have renamed the family Occ, for outer membrane carboxylate channels. We further show that Occ channels can be divided into two subfamilies, based on their very different substrate specificities. Our results rationalize how certain bacteria can efficiently take up a variety of substrates under nutrient-poor conditions without compromising membrane permeability. In addition, they explain how channel inactivation in response to antibiotics can cause resistance but does not lead to decreased fitness.
authors.affiliation: University of Massachusetts Medical School, Program in Molecular Medicine, Worcester, Massachusetts, United States of America.
authors.forename: Elif
authors.initials: E
authors.lastname: Eren
authors.forename: Jagamya
authors.initials: J
authors.lastname: Vijayaraghavan
authors.forename: Jiaming
authors.initials: J
authors.lastname: Liu
authors.forename: Belete R
authors.initials: BR
authors.lastname: Cheneke
authors.forename: Debra S
authors.initials: DS
authors.lastname: Touw
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Lepore
authors.forename: Mridhu
authors.initials: M
authors.lastname: Indic
authors.forename: Liviu
authors.initials: L
authors.lastname: Movileanu
authors.forename: Bert
authors.initials: B
authors.lastname: van den Berg
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D017124:Conserved Sequence / Q000235:genetics; D018360:Crystallography, X-Ray; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D005810:Multigene Family; D018272:Porins / Q000737:chemistry / Q000378:metabolism*; D016062:Porosity / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D021381:Protein Transport / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism*; D013379:Substrate Specificity / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D007473:Ion Channels; D018272:Porins; C077157:OprD protein, Pseudomonas aeruginosa