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The proposed<jats:italic>misR<\/jats:italic>\/<jats:italic>misS<\/jats:italic>(or<jats:italic>phoP<\/jats:italic>\/<jats:italic>phoQ<\/jats:italic>) system is one of four two-component systems of the obligate human pathogen<jats:italic>Neisseria meningitidis<\/jats:italic>. Inactivation of this system results in loss of phosphorylation of the lipooligosaccharide inner core and causes attenuation in a mouse model of meningococcal infection. MisR and the cytoplasmic domain of MisS were purified as His<jats:sub>6<\/jats:sub>and maltose binding protein fusion proteins, respectively. The MisS fusion was shown to be autophosphorylated in the presence of ATP, and the phosphoryl group was subsequently transferred to MisR. The phosphotransfer reaction was halted with a MisR\/D52A mutation, while a MisS\/H246A mutation prevented autophosphorylation. Specific interaction of phosphorylated MisR (MisR\u223cP) and MisR with the<jats:italic>misR<\/jats:italic>promoter was demonstrated by gel mobility shift assays, where MisR\u223cP exhibited higher affinity than did the nonphosphorylated protein. The transcriptional start site of the<jats:italic>misRS<\/jats:italic>operon was mapped, and DNase I protection assays revealed that MisR interacted with a 15-bp region upstream of the transcriptional start site that shared no similarity to binding motifs of other two-component systems. Transcriptional reporter studies suggested that MisR phosphorylation is critical for the autoinduction of the<jats:italic>misRS<\/jats:italic>operon. Limited Mg<jats:sup>2+<\/jats:sup>concentration failed to induce expression of the<jats:italic>misRS<\/jats:italic>operon, which is the only operon now proven to be under the direct control of the MisRS two-component system. Thus, these results indicate that the meningococcal MisRS system constitutes a functional signal transduction circuit and that both components are critical in the autoregulation of their expression.<\/jats:p>","DOI":"10.1128\/jb.00264-06","type":"journal-article","created":{"date-parts":[[2006,6,30]],"date-time":"2006-06-30T23:17:58Z","timestamp":1151709478000},"page":"5055-5065","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["Autoregulation of the MisR\/MisS Two-Component Signal Transduction System in<i>Neisseria meningitidis<\/i>"],"prefix":"10.1128","volume":"188","author":[{"given":"Yih-Ling","family":"Tzeng","sequence":"first","affiliation":[{"name":"Department of Medicine, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoliu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojia","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Emory University School of Medicine, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corie","family":"Noble","sequence":"additional","affiliation":[{"name":"Laboratories of Microbial Pathogenesis, Department of Veterans Affairs Medical Center, Decatur, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Medicine, Emory University School of Medicine, Atlanta, Georgia"},{"name":"Laboratories of Microbial Pathogenesis, Department of Veterans Affairs Medical Center, Decatur, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35006655"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/BF02821329","volume":"3","year":"1995","unstructured":"Barik, S. 1995. 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