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To gain a better understanding of how pH may affect binding to the receptor, we have investigated the kinetics of binding as a function of pH to the full\u2010length monomeric PA and to two variants: a 2\u2010fluorohistidine\u2010labeled PA (2\u2010FHisPA), which is \u223c1 pH unit more stable to variations in pH than WT, and an \u223c1 pH unit less stable variant in which Trp346 in the domain 2\u03b2<jats:sub>3<\/jats:sub>\u20102\u03b2<jats:sub>4<\/jats:sub> loop is substituted with a Phe (W346F). We show using stopped\u2010flow fluorescence that the binding rate increases as the pH is lowered for all proteins, with little influence on the rate of dissociation. In addition, we have crystallized PA and the two variants and examine the influence of pH on structure. In contrast to previous X\u2010ray studies, the domain 2\u03b2<jats:sub>3<\/jats:sub>\u20102\u03b2<jats:sub>4<\/jats:sub> loop undergoes little change in structure from pH \u223c8 to 5.5 for the WT protein, but for the 2\u2010FHis labeled and W346F mutant there are changes in structure consistent with previous X\u2010ray studies. In accord with pH stability studies, we find that the average <jats:italic>B<\/jats:italic>\u2010factor values increase by \u223c20\u201330% for all three proteins at low pH. Our results suggest that for the full\u2010length PA, low pH increases the binding affinity, likely through a change in structure that favors a more \u201cbound\u2010like\u201d conformation.<\/jats:p>","DOI":"10.1002\/pro.2136","type":"journal-article","created":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T10:59:19Z","timestamp":1343818759000},"page":"1467-1480","source":"Crossref","is-referenced-by-count":14,"title":["pH effects on binding between the anthrax protective antigen and the host cellular receptor CMG2"],"prefix":"10.1002","volume":"21","author":[{"given":"Maheshinie","family":"Rajapaksha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Lovell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blythe E.","family":"Janowiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran 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