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Specific binding and internalization of BoNT\/A into neuronal cells is mediated by its binding domain (H\n                    <jats:sub>C<\/jats:sub>\n                    \/A), which binds to gangliosides, including GT1b, and protein cell surface receptors, including SV2. Previously, recombinant H\n                    <jats:sub>C<\/jats:sub>\n                    \/A was also shown to bind to FGFR3. As FGFR dimerization is an indirect measure of ligand-receptor binding, an FCS &amp; TIRF receptor dimerization assay was developed to measure rH\n                    <jats:sub>C<\/jats:sub>\n                    \/A-induced dimerization of fluorescently tagged FGFR subtypes (FGFR1-3) in cells. rH\n                    <jats:sub>C<\/jats:sub>\n                    \/A dimerized FGFR subtypes in the rank order FGFR3c (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u2248 27\u00a0nM)\u2009&gt;\u2009FGFR2b (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u2248 70\u00a0nM)\u2009&gt;\u2009FGFR1c (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u2248 163\u00a0nM); rH\n                    <jats:sub>C<\/jats:sub>\n                    \/A dimerized FGFR3c with similar potency as the native FGFR3c ligand, FGF9 (EC\n                    <jats:sub>50<\/jats:sub>\n                    \u2248 18\u00a0nM). Mutating the ganglioside binding site in H\n                    <jats:sub>C<\/jats:sub>\n                    \/A, or removal of GT1b from the media, resulted in decreased dimerization. Interestingly, reduced dimerization was also observed with an SV2 mutant variant of H\n                    <jats:sub>C\/<\/jats:sub>\n                    A. Overall, the results suggest that the FCS &amp; TIRF receptor dimerization assay can assess FGFR dimerization with known and novel ligands and support a model wherein H\n                    <jats:sub>C<\/jats:sub>\n                    \/A, either directly or indirectly, interacts with FGFRs and induces receptor dimerization.\n                  <\/jats:p>","DOI":"10.1038\/s41598-021-87331-7","type":"journal-article","created":{"date-parts":[[2021,4,9]],"date-time":"2021-04-09T06:07:47Z","timestamp":1617948467000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Characterization of clostridium botulinum neurotoxin serotype A (BoNT\/A) and fibroblast growth factor receptor interactions using novel receptor dimerization assay"],"prefix":"10.1038","volume":"11","author":[{"given":"Nicholas G.","family":"James","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiazah","family":"Malik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethany J.","family":"Sanstrum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Rh\u00e9aume","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron S.","family":"Broide","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Jameson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Brideau-Andersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitte S.","family":"Jacky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,9]]},"reference":[{"key":"87331_CR1","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.2217\/fmb.09.72","volume":"4","author":"MR Popoff","year":"2009","unstructured":"Popoff, M. 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