Three-finger toxins

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Erabutoxin A, a three-finger toxin
Erabutoxin A, a three-finger toxin
Erabutoxin A , a neurotoxin in the 3FTx family. The three "fingers" are marked I, II and III and the four conserved disulfide bonds are shown in yellow.

Existing structure data : PDB  1QKD

Mass / length primary structure 83 amino acids , 9,137 Da
Identifier
External IDs

Three-finger toxins (3FTx for short) are a family of non-enzymatic polypeptides found in snake venoms . These toxins have the three-finger protein domain and therefore belong to the three-finger proteins , all of which have similar protein folds , but are not all toxic. Three-finger toxins usually consist of around 60 to 74 amino acid residues and have three β-sheets in their core element , which are connected to a central core that contains four conserved disulfide bonds . Despite their conserved structure, three-finger toxin proteins have a wide range of pharmacological effects. Among other things, they have neurotoxic, cardiotoxic and anticoagulant properties. The complex relationship between the biochemical structure and the function of the three-finger toxins is largely the subject of basic research. Most of the members of the family are neurotoxins that act on cholinergic intercellular signaling; the alpha neurotoxins interact with the nicotinic acetylcholine receptors (nAChRs), the kappa bungarotoxins with neuronal nAChRs and muscarinic toxins with muscarinic acetylcholine receptors (mAChRs).

structure

The three-finger toxins are defined by a common tertiary structure consisting of three β-sheet containing loops (the "fingers", referred to as loops I, II, and III) protruding from a small hydrophobic core with four conserved disulfide bonds. The proteins are typically 60-74 amino acid residues in length, but some have additional N- or C-terminal extensions. An additional disulfide bond can be present in either Loop I or Loop II. The family can be roughly divided into three classes:

  • short chain toxins have under 66 amino acid residues and four core disulfide bonds.
  • long chain toxins have at least 66 amino acid residues, a disulfide bond in loop II, and possibly a C-terminal extension.
  • non-conventional toxins have a disulfide bond in loop I and possibly a terminal extension.

Individual evidence

  1. ↑ V. Nastopoulos, PN Kanellopoulos, D. Tsernoglou: Structure of Dimeric and Monomeric erabutoxin a Refined at 1.5 A resolution . September 1, 1998, doi : 10.1107 / s0907444998005125 , PMID 9757111 (English, nih.gov ).
  2. ↑ a b c d R. Manjunatha Kini, Robin Doley: Structure, Function and Evolution of Three-Finger Toxins: Mini Proteins With Multiple Targets . November 2010, doi : 10.1016 / j.toxicon.2010.07.010 , PMID 20670641 (English, nih.gov ).
  3. ↑ Pascal Kessler, Pascale Marchot, Marcela Silva, Denis Servent: The Three-Finger Toxin Fold: A Multifunctional Structural Scaffold Able to Modulate Cholinergic Functions . doi : 10.1111 / jnc.13975 , PMID 28326549 (English, nih.gov ).
  4. ^ Snake three-finger toxin family. In: venomzone.expasy.org. Retrieved January 14, 2020 .