{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T07:33:55Z","timestamp":1790667235490,"version":"4.1.0"},"reference-count":30,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5735","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2005,7,29]]},"abstract":"<jats:p>The protective antigen component of anthrax toxin forms a homoheptameric pore in the endosomal membrane, creating a narrow passageway for the enzymatic components of the toxin to enter the cytosol. We found that, during conversion of the heptameric precursor to the pore, the seven phenylalanine-427 residues converged within the lumen, generating a radially symmetric heptad of solvent-exposed aromatic rings. This \u201c\u03c6-clamp\u201d structure was required for protein translocation and comprised the major conductance-blocking site for hydrophobic drugs and model cations. We conclude that the \u03c6 clamp serves a chaperone-like function, interacting with hydrophobic sequences presented by the protein substrate as it unfolds during translocation.<\/jats:p>","DOI":"10.1126\/science.1113380","type":"journal-article","created":{"date-parts":[[2005,7,28]],"date-time":"2005-07-28T17:43:39Z","timestamp":1122572619000},"page":"777-781","source":"Crossref","is-referenced-by-count":272,"title":["A Phenylalanine Clamp Catalyzes Protein Translocation Through the Anthrax Toxin Pore"],"prefix":"10.1126","volume":"309","author":[{"given":"Bryan A.","family":"Krantz","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman A.","family":"Melnyk","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Juris","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Borden","family":"Lacy","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengyan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA."}],"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, USA."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA."}],"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, USA."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.19.111301.140655"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)38364-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi990792d"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.7.2209"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi972657b"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0119518"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.09.067"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi981436i"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.104.050864"},{"key":"e_1_3_2_11_2","unstructured":"We define the membrane potential as \u0394\u03c8 = \u03c8 cis - \u03c8 trans where \u03c8 trans = 0 mV. The cis side is the side to which PA 63 and LF N are added."},{"key":"e_1_3_2_12_2","unstructured":"Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008309200"},{"key":"e_1_3_2_14_2","unstructured":"Mutation of several other sites in domain 2 were also shown to block translocation but these prevented pore formation ( 12 25 )."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.51.2.199"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405754101"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.96.5.905"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(02)02027-8"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.5560010204"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.104.050336"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(08)60608-7"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/35079500"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5360.69"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02218"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7824948"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2436299100"},{"key":"e_1_3_2_27_2","unstructured":"B. A. Krantz R. A. Melnyk R. J. Collier A. Finkelstein unpublished data."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405405101"},{"key":"e_1_3_2_29_2","unstructured":"Materials and methods are available as supporting material on Science Online."},{"key":"e_1_3_2_30_2","unstructured":"Translocation of LF N (and full-length LF) was greatly accelerated when the pH on the trans side was greater than that on the cis side ( 26 )."},{"key":"e_1_3_2_31_2","unstructured":"R.J.C. is cofounder member of the scientific advisory board and equity holder in PharmAthene Inc. a startup company that investigates countermeasures against anthrax and other bioterrorism agents. We thank K. J. Oh for EPR data acquisition; R. Ross at the New England Research Center of Excellence Biomolecule Production Core as well as R. Pimental L. Greene and H. Lin for their assistance in purifying and generating PA mutants; and W. Hubbell T. Sosnick and A. Johnson for useful discussions. This work was supported by a National Research Service Award fellowship AI062204 (B.A.K.) and NIH grants AI022021 (R.J.C.) and GM29210 (A.F.)."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1113380","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T21:42:54Z","timestamp":1704836574000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1113380"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,7,29]]},"references-count":30,"journal-issue":{"issue":"5735","published-print":{"date-parts":[[2005,7,29]]}},"alternative-id":["10.1126\/science.1113380"],"URL":"https:\/\/doi.org\/10.1126\/science.1113380","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1027194.326657","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1027194.329617","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1027194.348417","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,7,29]]}}}