{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:03:22Z","timestamp":1790420602284,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"48","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,11,30]]},"abstract":"\n Entry of the enzymatic components of anthrax toxin [lethal factor (LF) and edema factor] into the cytosol of mammalian cells depends on the ability of the activated protective antigen (PA\n 63<\/jats:sub>\n ) component to form a channel (pore) in the membrane of an acidic intracellular compartment. To investigate the mechanism of translocation, we characterized N-terminally truncated forms of the PA\n 63<\/jats:sub>\n -binding domain of LF (LF\n N<\/jats:sub>\n ). Deleting 27 or 36 residues strongly inhibited acid-triggered translocation of LF\n N<\/jats:sub>\n across the plasma membrane of CHO-K1 cells and ablated the protein's ability to block PA\n 63<\/jats:sub>\n channels in planar lipid bilayers at a small positive voltage (+20 mV). Fusing a H\n 6<\/jats:sub>\n -tag to the N terminus of the truncated proteins restored both translocation and channel-blocking activities. At +20 mV, N-terminal H\n 6<\/jats:sub>\n and biotin tags were accessible to Ni\n 2+<\/jats:sup>\n and streptavidin, respectively, added to the trans compartment of a planar bilayer. On the basis of these findings, we propose that the N terminus of PA\n 63<\/jats:sub>\n -bound LF or edema factor enters the PA\n 63<\/jats:sub>\n -channel under the influence of acidic pH and a positive transmembrane potential and initiates translocation in an N- to C-terminal direction.\n <\/jats:p>","DOI":"10.1073\/pnas.0405754101","type":"journal-article","created":{"date-parts":[[2004,11,17]],"date-time":"2004-11-17T20:25:13Z","timestamp":1100723113000},"page":"16756-16761","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":112,"title":["Evidence that translocation of anthrax toxin's lethal factor is initiated by entry of its N terminus into the protective antigen channel"],"prefix":"10.1073","volume":"101","author":[{"given":"Sen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115; and Department of Physiology and Biophysics and Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Finkelstein","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115; and Department of Physiology and Biophysics and Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. John","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115; and Department of Physiology and Biophysics and Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,11,17]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.19.111301.140655"},{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","unstructured":"Leppla S. H. (2000) in Bacterial Protein Toxins eds. Aktories K. & Just I. 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