Affiliations

Professor, Microbiology, Immunology & Molecular Genetics

Member, Biochemistry, Biophysics & Structural Biology GPB Home Area

The McEvoy laboratory is focused on developing an understanding of how organisms handle metal ions. Organisms can face highly varying levels of metal ions through their environment or diet, and metal ion concentrations in cells must be carefully regulated. Some metal cations, such as copper, cobalt, and nickel, are essential in trace amounts, though toxic at higher concentrations. Other metal ions, such as silver and mercury, do not fulfill any biological requirements but instead can interfere with proper cellular function even at relatively low concentrations. We are particularly interested in understanding how bacteria maintain metal ion homeostasis as metal ions can serve as broad spectrum biocides. The emergence of drug-resistant bacteria through the overuse of antibiotics has brought a newfound interest in understanding how metal ions function as biocides and how bacteria respond when challenged with high metal ion concentrations as these may ultimately lead to new methods for combating disease. We are applying multidisciplinary approaches to understand a variety of interests including 1) how metal ions are discriminated 2) structural changes controlling protein function and 3) organismal responses to metal ions.

Affandi Trisiani, Issaian Aaron V, McEvoy Megan M The Structure of the Periplasmic Sensor Domain of the Histidine Kinase CusS Shows Unusual Metal Ion Coordination at the Dimeric Interface. Biochemistry. 2016; 55(37): 5296-306. Cantu-Bustos J Enrique, Vargas-Cortez Teresa, Morones-Ramirez Jose Ruben, Balderas-Renteria Isaias, Galbraith David W, McEvoy Megan M, Zarate Xristo Expression and purification of recombinant proteins in Escherichia coli tagged with the metal-binding protein CusF. Protein expression and purification. 2016; 121: 61-5. Chacón Kelly N, Mealman Tiffany D, McEvoy Megan M, Blackburn Ninian J Tracking metal ions through a Cu/Ag efflux pump assigns the functional roles of the periplasmic proteins. Proceedings of the National Academy of Sciences of the United States of America. 2014; 111(43): 15373-8. Gudipaty Swapna A, McEvoy Megan M The histidine kinase CusS senses silver ions through direct binding by its sensor domain. Biochimica et biophysica acta. 2014; 1844(9): 1656-61. Padilla-Benavides Teresita, George Thompson Alayna M, McEvoy Megan M, Argüello José M Mechanism of ATPase-mediated Cu+ export and delivery to periplasmic chaperones: the interaction of Escherichia coli CopA and CusF. The Journal of biological chemistry. 2014; 289(30): 20492-501. Jayakanthan Samuel, Roberts Sue A, Weichsel Andrzej, Argüello José M, McEvoy Megan M Conformations of the apo-, substrate-bound and phosphate-bound ATP-binding domain of the Cu(II) ATPase CopB illustrate coupling of domain movement to the catalytic cycle. Bioscience reports. 2012; 32(5): 443-53. Mealman Tiffany D, Zhou Mowei, Affandi Trisiani, Chacón Kelly N, Aranguren Mariana E, Blackburn Ninian J, Wysocki Vicki H, McEvoy Megan M N-terminal region of CusB is sufficient for metal binding and metal transfer with the metallochaperone CusF. Biochemistry. 2012; 51(34): 6767-75. Mealman Tiffany D, Blackburn Ninian J, McEvoy Megan M Metal export by CusCFBA, the periplasmic Cu(I)/Ag(I) transport system of Escherichia coli. Current topics in membranes. 2012; 69(1): 163-96. Gudipaty Swapna Aravind, Larsen Andrew S, Rensing Christopher, McEvoy Megan M Regulation of Cu(I)/Ag(I) efflux genes in Escherichia coli by the sensor kinase CusS. FEMS microbiology letters. 2012; 330(1): 30-7. McEvoy Megan M, Rensing Christopher Biometals 2010 (Tucson, Arizona, USA). Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. 2011; 24(3): 377-8. Kim Eun-Hae, Nies Dietrich H, McEvoy Megan M, Rensing Christopher Switch or funnel: how RND-type transport systems control periplasmic metal homeostasis. Journal of bacteriology. 2011; 193(10): 2381-7. Mealman Tiffany D, Bagai Ireena, Singh Pragya, Goodlett David R, Rensing Christopher, Zhou Hongjun, Wysocki Vicki H, McEvoy Megan M Interactions between CusF and CusB identified by NMR spectroscopy and chemical cross-linking coupled to mass spectrometry. Biochemistry. 2011; 50(13): 2559-66. Conroy Otakuye, Kim Eun-Hae, McEvoy Megan M, Rensing Christopher Differing ability to transport nonmetal substrates by two RND-type metal exporters. FEMS microbiology letters. 2010; 308(2): 115-22. Kim Eun-Hae, Rensing Christopher, McEvoy Megan M Chaperone-mediated copper handling in the periplasm. Natural product reports. 2010; 27(5): 711-9. Kim Eun-Hae, Charpentier Xavier, Torres-Urquidy Oscar, McEvoy Megan M, Rensing Christopher The metal efflux island of Legionella pneumophila is not required for survival in macrophages and amoebas. FEMS microbiology letters. 2009; 301(2): 164-70. Quaranta Davide, McEvoy Megan M, Rensing Christopher Site-directed mutagenesis identifies a molecular switch involved in copper sensing by the histidine kinase CinS in Pseudomonas putida KT2440. Journal of bacteriology. 2009; 191(16): 5304-11. Loftin Isabell R, Blackburn Ninian J, McEvoy Megan M Tryptophan Cu(I)-pi interaction fine-tunes the metal binding properties of the bacterial metallochaperone CusF. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 2009; 14(6): 905-12. Bagai Ireena, Rensing Christopher, Blackburn Ninian J, McEvoy Megan M Direct metal transfer between periplasmic proteins identifies a bacterial copper chaperone. Biochemistry. 2008; 47(44): 11408-14. Bagai Ireena, Liu Wenbo, Rensing Christopher, Blackburn Ninian J, McEvoy Megan M Substrate-linked conformational change in the periplasmic component of a Cu(I)/Ag(I) efflux system. The Journal of biological chemistry. 2007; 282(49): 35695-702. Loftin Isabell R, Franke Sylvia, Blackburn Ninian J, McEvoy Megan M Unusual Cu(I)/Ag(I) coordination of Escherichia coli CusF as revealed by atomic resolution crystallography and X-ray absorption spectroscopy. Protein science : a publication of the Protein Society. 2007; 16(10): 2287-93. Kittleson Joshua T, Loftin Isabell R, Hausrath Andrew C, Engelhardt Kevin P, Rensing Christopher, McEvoy Megan M Periplasmic metal-resistance protein CusF exhibits high affinity and specificity for both CuI and AgI. Biochemistry. 2006; 45(37): 11096-102. Loftin Isabell R, Franke Sylvia, Roberts Sue A, Weichsel Andrzej, Héroux Annie, Montfort William R, Rensing Christopher, McEvoy Megan M A novel copper-binding fold for the periplasmic copper resistance protein CusF. Biochemistry. 2005; 44(31): 10533-40. Astashkin Andrei V, Raitsimring Arnold M, Walker F Ann, Rensing Christopher, McEvoy Megan M Characterization of the copper(II) binding site in the pink copper binding protein CusF by electron paramagnetic resonance spectroscopy. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry. 2005; 10(3): 221-30. Dyer Collin M, Quillin Michael L, Campos Andres, Lu Justine, McEvoy Megan M, Hausrath Andrew C, Westbrook Edwin M, Matsumura Philip, Matthews Brian W, Dahlquist Frederick W Structure of the constitutively active double mutant CheYD13K Y106W alone and in complex with a FliM peptide. Journal of molecular biology. 2004; 342(4): 1325-35.