The three-finger toxin fold: a multifunctional structural scaffold able to modulate cholinergic functions.
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.
Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), IBITECS, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
Pascal
P
Kessler
Aix-Marseille Université/Centre National de la Recherche Scientifique, Architecture et Fonction des Macromolécules Biologiques laboratory, Faculté des Sciences Campus Luminy, Marseille, France.
Pascale
P
Marchot
Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), IBITECS, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.|Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Marcela
M
Silva
Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), IBITECS, CEA, Université Paris-Saclay, Gif-sur-Yvette, France.
Denis
D
Servent
D000109:Acetylcholine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012910:Snake Venoms / Q000633:toxicity*; D014118:Toxins, Biological / Q000378:metabolism*
D018678:Cholinergic Agents; D011976:Receptors, Muscarinic; D012910:Snake Venoms; D014118:Toxins, Biological; D000109:Acetylcholine
acetylcholinesterase; cholinergic system; muscarinic acetylcholine receptor; nicotinic acetylcholine receptor; snake venom; three-finger fold toxin