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Once the toxin binds to its cell surface receptors it is internalized into the cell and traffics through Rab5\u2010 and Rab7\u2010associated endosomal vesicles. Following acidification of the vesicle lumen, PA63 undergoes a dynamic change forming a beta\u2010barrel that inserts into and forms a pore through the endosomal membrane. It is widely recognized that LF, and the related fusion protein LFnDTA, must be completely denatured in order to transit through the PA63 formed pore and enter the eukaryotic cell cytosol. We demonstrate by protease protection assays that the molecular chaperone GRP78 mediates the unfolding of LFnDTA and LF at neutral pH and thereby converts these proteins from a trypsin resistant to sensitive conformation. We have used immunoelectron microscopy and gold\u2010labelled antibodies to demonstrate that both GRP78 and GRP94 chaperones are present in the lumen of endosomal vesicles. Finally, we have used siRNA to demonstrate that knock\u2010down of GRP78 results in the emergence of resistance to anthrax lethal toxin and oedema toxin action.<\/jats:p>","DOI":"10.1111\/j.1365-2958.2011.07770.x","type":"journal-article","created":{"date-parts":[[2011,7,29]],"date-time":"2011-07-29T10:17:13Z","timestamp":1311934633000},"page":"1390-1401","source":"Crossref","is-referenced-by-count":18,"title":["GRP78(BiP) facilitates the cytosolic delivery of anthrax lethal factor (LF) <i>in vivo<\/i> and functions as an unfoldase <i>in vitro<\/i>"],"prefix":"10.1111","volume":"81","author":[{"given":"Alfred 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