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This fold is characterized by three distinct loops rich in \u03b2\u2010strands and emerging from a dense, globular core reticulated by four highly conserved disulfide bridges. The number and diversity of receptors, channels, and enzymes identified as targets of three\u2010finger fold toxins is increasing continuously. Such manifold diversity highlights the specific adaptability of this fold for generating pleiotropic functions. Although this toxin superfamily disturbs many biological functions by interacting with a large diversity of molecular targets, the most significant target is the cholinergic system. By blocking the activity of the nicotinic and muscarinic acetylcholine receptors or by inhibiting the enzyme acetylcholinesterase, three\u2010finger fold toxins interfere most drastically with neuromuscular junction functioning. Several of these toxins have become powerful pharmacological tools for studying the function and structure of their molecular targets. Most importantly, since dysfunction of these receptors\/enzyme is involved in many diseases, exploiting the three\u2010finger scaffold to create novel, highly specific therapeutic agents may represent a major future endeavor.<\/jats:p><jats:p><jats:bold>This is an article for the<\/jats:bold>\u00a0<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/journal\/10.1111\/(ISSN)1471-4159\/homepage\/special_issues.htm\">special issue XVth International Symposium on Cholinergic Mechanisms<\/jats:ext-link>.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13975-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13975","type":"journal-article","created":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T12:01:04Z","timestamp":1490184064000},"page":"7-18","source":"Crossref","is-referenced-by-count":105,"title":["The three\u2010finger toxin fold: a multifunctional structural scaffold able to modulate cholinergic functions"],"prefix":"10.1111","volume":"142","author":[{"given":"Pascal","family":"Kessler","sequence":"first","affiliation":[{"name":"Service d'Ing\u00e9nierie Mol\u00e9culaire des Prot\u00e9ines (SIMOPRO) IBITECS CEA Universit\u00e9 Paris\u2010Saclay Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Marchot","sequence":"additional","affiliation":[{"name":"Aix\u2010Marseille Universit\u00e9\/Centre National de la Recherche Scientifique Architecture et Fonction des Macromol\u00e9cules Biologiques laboratory Facult\u00e9 des Sciences Campus Luminy Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Silva","sequence":"additional","affiliation":[{"name":"Service d'Ing\u00e9nierie Mol\u00e9culaire des Prot\u00e9ines (SIMOPRO) IBITECS CEA Universit\u00e9 Paris\u2010Saclay Gif\u2010sur\u2010Yvette France"},{"name":"Institute of Biological Sciences Federal University of Minas Gerais Belo Horizonte Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Servent","sequence":"additional","affiliation":[{"name":"Service d'Ing\u00e9nierie Mol\u00e9culaire des Prot\u00e9ines (SIMOPRO) IBITECS CEA Universit\u00e9 Paris\u2010Saclay Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(88)90025-0"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.49.34851"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M909746199"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2005.23973.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.20661"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2007.06.026"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2007.01.003"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1994.1357"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90128-0"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600620"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2016.04.014"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(93)90027-B"},{"key":"e_1_2_7_14_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0031-6997(24)01362-0","article-title":"International Union of Pharmacology. 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