The three-finger toxin fold: a multifunctional structural scaffold able to modulate cholinergic functions
2017
Kessler, Pascal | Marchot, Pascale | Silva, Marcela | Servent, Denis | Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) ; Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Architecture et fonction des macromolécules biologiques (AFMB) ; Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS) | Institut de Biologie et de Technologies de Saclay (IBITECS) ; Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay | ANR-15-CE07-0022,EasyMiniProt,Outils chimiques innovants pour la synthèse de peptides riche en ponts disulfure , une classe émergente de molécules d'intêrêt thérapeutique(2015)
International audience
显示更多 [+] 显示较少 [-]英语. Three-finger fold toxins are miniproteins frequently found in Elapidae snake venoms. This fold is characterized by three distinct loops rich in β-strands 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-finger 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-finger 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-finger scaffold to create novel, highly specific therapeutic agents may represent a major future endeavor. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.
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