{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:10:50Z","timestamp":1789539050100,"version":"build-2803163510"},"reference-count":58,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,11,19]],"date-time":"2014-11-19T00:00:00Z","timestamp":1416355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2014,11,19]],"date-time":"2014-11-19T00:00:00Z","timestamp":1416355200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cellular Microbiology"],"published-print":{"date-parts":[[2015,2]]},"abstract":"Summary<\/jats:title>\n \n \n C<\/jats:italic>\n <\/jats:styled-content>\n lostridium perfringens<\/jats:italic>\n iota toxin is a binary toxin that is organized into enzyme (\n I<\/jats:styled-content>\n a) and binding (\n I<\/jats:styled-content>\n b) components.\n I<\/jats:styled-content>\n b forms channels in lipid bilayers and mediates the transport of Ia into the target cells. Here we show that Ib residues 334\u2013359 contain a conserved pattern of alternating hydrophobic and hydrophilic residues forming two amphipathic \u03b2\u2010strands involved in membrane insertion and channel formation. This stretch of amino acids shows remarkable structural and functional analogies with the \u03b2\u2010pore\u2010forming domain of\n \n C<\/jats:italic>\n <\/jats:styled-content>\n .\u2009perfringens<\/jats:italic>\n epsilon toxin. Several mutations within the two amphipathic \u03b2\u2010strands affected pore formation, single\u2010channel conductance and ion selectivity (\n S339E<\/jats:styled-content>\n \u2010\n S341E<\/jats:styled-content>\n ,\n Q345H N346E<\/jats:styled-content>\n ) confirming their involvement in channel formation.\n F454<\/jats:styled-content>\n of\n I<\/jats:styled-content>\n b corresponds to the \u03a6\u2010clamp\n F427<\/jats:styled-content>\n of anthrax protective antigen and\n F428<\/jats:styled-content>\n of\n C2II<\/jats:styled-content>\n binary toxins. The mutation\n F454A<\/jats:styled-content>\n resulted in a loss of cytotoxicity and strong increase in single\u2010channel conductance (500\u2009pS as compared with 85\u2009pS in 1\u2009M\n KCl<\/jats:styled-content>\n ) with a slight decrease in cation selectivity, indicating that the \u03a6\u2010clamp is highly conserved and crucial for binary toxin activity. In contrast, the mutants\n Q367D<\/jats:styled-content>\n ,\n N430D<\/jats:styled-content>\n ,\n L443E<\/jats:styled-content>\n had no or only minor effects on Ib properties, while\n T360I<\/jats:styled-content>\n ,\n T360A<\/jats:styled-content>\n and\n T360W<\/jats:styled-content>\n caused a dramatic effect on ion selectivity and single\u2010channel conductance, indicating gross disturbance of the oligomer structure. This suggests that, at least in the iota toxin family,\n T<\/jats:styled-content>\n 360 has a structural role in the pore organization. Moreover, introduction of charged residues within the channel (\n S339E<\/jats:styled-content>\n \u2010\n S341E<\/jats:styled-content>\n ) or in the vestibule (\n Q367D<\/jats:styled-content>\n ,\n N430D<\/jats:styled-content>\n and\n L443E<\/jats:styled-content>\n ) had virtually no effect on chloroquine or\n I<\/jats:styled-content>\n a binding, whereas\n F454A<\/jats:styled-content>\n ,\n T360I<\/jats:styled-content>\n ,\n T360A<\/jats:styled-content>\n and\n T360W<\/jats:styled-content>\n strongly decreased the chloroquine and Ia affinity to\n I<\/jats:styled-content>\n b. These results support that distinct residues within the vestibule interact with chloroquine and Ia or are responsible for channel structure, while the channel lining amino acids play a less important role.\n <\/jats:p>","DOI":"10.1111\/cmi.12366","type":"journal-article","created":{"date-parts":[[2014,9,30]],"date-time":"2014-09-30T03:39:56Z","timestamp":1412048396000},"page":"288-302","source":"Crossref","is-referenced-by-count":27,"title":["Residues involved in the pore\u2010forming activity of the\n \n C<\/i>\n <\/scp>\n lostridium perfringens<\/i>\n iota toxin"],"prefix":"10.1155","volume":"17","author":[{"given":"Oliver","family":"Knapp","sequence":"first","affiliation":[{"name":"Institut Pasteur, Bact\u00e9ries ana\u00e9robies et Toxines 28 rue du Dr Roux, F\u201075724 Paris Cedex 15 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elke","family":"Maier","sequence":"additional","affiliation":[{"name":"Rudolf\u2010Virchow\u2010Center, DFG\u2010Research Center for Experimental Biomedicine University of W\u00fcrzburg Versbacher Str. 9 D\u201097078 W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Waltenberger","sequence":"additional","affiliation":[{"name":"School of Engineering and Science Jacobs University Bremen Campusring 1 D\u201028759 Bremen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Mazuet","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Bact\u00e9ries ana\u00e9robies et Toxines 28 rue du Dr Roux, F\u201075724 Paris Cedex 15 France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Benz","sequence":"additional","affiliation":[{"name":"Rudolf\u2010Virchow\u2010Center, DFG\u2010Research Center for Experimental Biomedicine University of W\u00fcrzburg Versbacher Str. 9 D\u201097078 W\u00fcrzburg Germany"},{"name":"School of Engineering and Science Jacobs University Bremen Campusring 1 D\u201028759 Bremen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel R.","family":"Popoff","sequence":"additional","affiliation":[{"name":"Institut Pasteur, Bact\u00e9ries ana\u00e9robies et Toxines 28 rue du Dr Roux, F\u201075724 Paris Cedex 15 France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/322390a0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0671fje"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2003.08.044"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109167200"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.68.3.373-402.2004"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi972657b"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.89.2.275"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(78)90269-9"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(89)90002-3"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.7.2209"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.5.2980-2987.2001"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi034199e"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305849200"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1042\/BC20050082"},{"key":"e_1_2_6_16_1","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.1128\/IAI.68.7.3848-3853.2000","article-title":"Clostridium perfringens iota\u2010toxin requires activation of both binding and enzymatic components for cytopathic activity","volume":"68","author":"Gibert M.","year":"2000","journal-title":"Infect Immun"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.02.041"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01527.x"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.10.6004-6011.2001"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2186-2193.2004"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.5.3066-3068.2004"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00710-09"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.07.037"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103939200"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2009.09.020"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113380"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023133"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi800615g"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012088445-2\/50023-8"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01318a036"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.4.2435-2441.2001"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1990.tb19448.x"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10254-004-0028-2"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709807200"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(86)90511-5"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.104.050336"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109772108"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.06378-11"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.61.12.5147-5156.1993"},{"key":"e_1_2_6_40_1","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1128\/iai.65.4.1402-1407.1997","article-title":"Production of a complete binary toxin (actin\u2010specific ADP\u2010ribosylating toxin) by Clostridium difficile CD196","volume":"65","author":"Perelle S.","year":"1997","journal-title":"Infect Immun"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.1997.tb10180.x"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010412200"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/385833a0"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(88)80435-2"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012088445-2\/50014-7"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.56.9.2299-2306.1988"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.09.002"},{"key":"e_1_2_6_48_1","doi-asserted-by":"crossref","first-page":"16706","DOI":"10.1016\/S0021-9258(19)89448-6","article-title":"Interaction of Clostridium botulinum C2 toxin with lipid bilayer membranes","volume":"269","author":"Schmid A.","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(89)90059-0"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.6.3475-3484.2000"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.54.3.683-688.1986"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20020566"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2011.00011"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800701105"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)01247-0"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0801215105"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006280"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051356"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.75.103004.142728"}],"container-title":["Cellular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcmi.12366","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cmi.12366","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cmi.12366","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cmi.12366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T05:05:15Z","timestamp":1775883915000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cmi.12366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,19]]},"references-count":58,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,2]]}},"alternative-id":["10.1111\/cmi.12366"],"URL":"https:\/\/doi.org\/10.1111\/cmi.12366","archive":["Portico"],"relation":{},"ISSN":["1462-5814"],"issn-type":[{"value":"1462-5814","type":"print"}],"subject":[],"published":{"date-parts":[[2014,11,19]]}}}