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Inquiries into the molecular mechanism of nanomachine\u2010catalyzed biopolymer transport have revealed that these machines are equipped with molecular parts, including adjustable clamps, levers, and adaptors, which interact favorably with substrate polypeptides. Biological nanomachines that catalyze protein transport, known as translocases, often require that their substrate proteins unfold before translocation. An unstructured protein chain is likely entropically challenging to bind, push, or pull in a directional manner, especially in a way that produces an unfolding force. A number of ingenious solutions to this problem are now evident in the anthrax toxin system, a model used to study protein translocation. Here we highlight molecular ratchets and current research on anthrax toxin translocation. A picture is emerging of proton\u2010gradient\u2010driven anthrax toxin translocation, and its associated ratchet mechanism likely applies broadly to other systems. We suggest a cyclical thermodynamic order\u2010to\u2010disorder mechanism (akin to a heat\u2010engine cycle) is central to underlying protein translocation: peptide substrates nonspecifically bind to molecular clamps, which possess adjustable affinities; polypeptide substrates compress into helical structures; these clamps undergo proton\u2010gated switching; and the substrate subsequently expands regaining its unfolded state conformational entropy upon translocation.<\/jats:p>","DOI":"10.1002\/pro.2052","type":"journal-article","created":{"date-parts":[[2012,2,28]],"date-time":"2012-02-28T15:01:49Z","timestamp":1330441309000},"page":"606-624","source":"Crossref","is-referenced-by-count":66,"title":["Ratcheting up protein translocation with anthrax toxin"],"prefix":"10.1002","volume":"21","author":[{"given":"Geoffrey K.","family":"Feld","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan A.","family":"Krantz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3,30]]},"reference":[{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07614.x"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(03)00010-1"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2004.09.011"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113752"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-060408-172623"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.09.020"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2008.12.002"},{"key":"e_1_2_10_9_2","volume-title":"Theory of heat","author":"Maxwell JC","year":"1871"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/009441c0"},{"key":"e_1_2_10_11_2","unstructured":"SullivanMV(1946) Activated amusement device. 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