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The cytoplasmic ATPase EpsE provides the energy for exoprotein secretion through ATP hydrolysis. EpsE contains a unique metal\u2010binding domain that coordinates zinc through a tetracysteine motif (CXXCX<jats:sub>29<\/jats:sub>CXXC), which is also present in type IV pilus assembly but not retraction ATPases. Deletion of the entire domain or substitution of any of the cysteine residues that coordinate zinc completely abrogates secretion in an EpsE\u2010deficient strain and has a dominant negative effect on secretion in the presence of wild\u2010type EpsE. Consistent with the in vivo data, chemical depletion of zinc from purified EpsE hexamers results in loss of in vitro ATPase activity. In contrast, exchanging the residues between the two dicysteines with those from the homologous ATPase XcpR from <jats:italic>Pseudomonas aeruginosa<\/jats:italic> does not have a significant impact on EpsE. These results indicate that, although the individual residues in the metal\u2010binding domain are generally interchangeable, zinc coordination is essential for the activity and function of EpsE.<\/jats:p>","DOI":"10.1002\/mbo3.376","type":"journal-article","created":{"date-parts":[[2016,5,11]],"date-time":"2016-05-11T03:43:03Z","timestamp":1462938183000},"page":"870-882","source":"Crossref","is-referenced-by-count":13,"title":["Zinc coordination is essential for the function and activity of the type II secretion ATPase EpsE"],"prefix":"10.1002","volume":"5","author":[{"given":"Chelsea S.","family":"Rule","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology University of Michigan Medical School Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcella","family":"Patrick","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Michigan Medical School Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jodi L.","family":"Camberg","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases Department of Medicine University of Maryland School of Medicine Rockville Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Maricic","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Michigan Medical School Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim G.","family":"Hol","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Biomolecular Structure Center University of Washington Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Sandkvist","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology University of Michigan Medical School Ann Arbor Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,5,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2005.02.061"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.701284"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.187.1.249-256.2005"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601481"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.2007\/011320-0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2005.09.005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1128\/JB.180.21.5591-5600.1998","article-title":"Endochitinase is transported to the extracellular milieu by the eps\u2010encoded general secretory pathway of Vibrio cholerae","volume":"180","author":"Connell T. 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