pubmed.ncbi.nlm.nih.gov

Spider Venom: Components, Modes of Action, and Novel Strategies in Transcriptomic and Proteomic Analyses - PubMed

  • ️Tue Jan 01 2019

Review

Spider Venom: Components, Modes of Action, and Novel Strategies in Transcriptomic and Proteomic Analyses

Nicolas Langenegger et al. Toxins (Basel). 2019.

Abstract

This review gives an overview on the development of research on spider venoms with a focus on structure and function of venom components and techniques of analysis. Major venom component groups are small molecular mass compounds, antimicrobial (also called cytolytic, or cationic) peptides (only in some spider families), cysteine-rich (neurotoxic) peptides, and enzymes and proteins. Cysteine-rich peptides are reviewed with respect to various structural motifs, their targets (ion channels, membrane receptors), nomenclature, and molecular binding. We further describe the latest findings concerning the maturation of antimicrobial, and cysteine-rich peptides that are in most known cases expressed as propeptide-containing precursors. Today, venom research, increasingly employs transcriptomic and mass spectrometric techniques. Pros and cons of venom gland transcriptome analysis with Sanger, 454, and Illumina sequencing are discussed and an overview on so far published transcriptome studies is given. In this respect, we also discuss the only recently described cross contamination arising from multiplexing in Illumina sequencing and its possible impacts on venom studies. High throughput mass spectrometric analysis of venom proteomes (bottom-up, top-down) are reviewed.

Keywords: Araneae; bioinformatics; mass spectrometry; neurotoxins; proteomics; spiders; transcriptomics; venomics.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1

Antimicrobial peptides (AMPs) and their proposed mechanism of action. (A) Model of interaction between an AMP and phospholipids. AMPs assume an amphipathic α-helical structure in proximity to cellular membranes. The hydrophobic side of the helix (white) inserts into the membrane and interacts with the phospholipid side chains. The positively charged side (blue) interacts with negatively charged lipid head groups. (B) Models of membranolytic actions of AMPs. (C) NMR-based 3D structures of two antimicrobial peptides from spider venom. Electrostatics were computed using PDB2PQR [70]. Blue surfaces represent positively charged surfaces; red negative charged; and white neutral.

Figure 2
Figure 2

Structural motifs of cysteine-rich spider venom peptides. Disulphide connected cysteines are numbered and disulphide bridges are shown in yellow. A linear schematic representation of the disulphide bridge pattern is shown below the corresponding 3D structure. (A) Inhibitor cystine knot motif. The disulphide bridge colored in orange penetrates the ring opened by the peptide backbone and the two other disulphide bridges. (B) Disulphide-directed β-hairpin motif. The disulphide bridge colored in blue is optional for this motif. (C) Kunitz-type motif. (D) Colipase or MIT1-like motif. (E) Helical arthropod-neuropeptide-derived motif.

Figure 3
Figure 3

Binding of neurotoxins to a voltage gated ion channel. Peptides are shown space filling, ion channels as cartoons with every domain in a different color. (A) Hydrophobic patch with surrounding ring of charged amino acids. Hydrophobic amino acids are shown in green, negatively charged in blue, and positively charged in red. (B) Four ProTx-2 toxins bound to the human NaV1.7 channel in side view. Toxin surface represents surface charge. Eye-icons and arrows indicate the viewing angel in panels B1 and B2. (B1) View on one voltage-sensing domain of the channel bound to the toxin from the inner side of the membrane towards outwards. (B2) View on the toxin-channel complex form the top. Helices of the voltage sensing domain are indicated with S1–S4.

Figure 4
Figure 4

3D structures and schematic structures of modular toxins (multi-domain toxins). Antimicrobial domains are highlighted in blue, disulphide bridges in yellow. (A) Neurotoxin-AMP. (B) AMP-neurotoxin. The structure of spiderine-1a is assembled from two experimental 3D structures of the N- and C-terminal toxin part, respectively. (C) Neurotoxin-neurotoxin. (D) AMP-AMP.

Figure 5
Figure 5

Maturing of venom peptides. (A) Stepwise schematic representation of the general maturing processes on the example of CsTx-13 (see panel D). (1) The Processing Quadruplet Motif (PQM) protease cleaves C-terminal of the Arg residue of the PQM or inverted Processing Quadruplet Motif (iPQM). (2) A so far uncharacterized carboxypeptidase subsequently removes the C-terminally exposed Arg if present, and (3) if a C-terminally exposed Gly is present, this is eliminated under formation of a C-terminal amide. (B–E) Schematic representation of chosen precursor sequences (top) and the corresponding mature sequences of neurotoxins. Maturing processes are indicated by arrows and triangles (see legend in the top right corner). (B) Precursor of a monomeric neurotoxin. (C,D) Precursors of heterodimeric neurotoxins. (E) N-terminal segment of a complex AMP precursor. Amino acids with positive side-chain charges at pH 7 are shown in blue, such with negative charges at pH 7 in red. All here shown precursors also comprise signal peptides which are not shown for reasons of space.

Similar articles

Cited by

References

    1. Calvete J.J. Venomics: Integrative venom proteomics and beyond. Biochem. J. 2017;474:611–634. doi: 10.1042/BCJ20160577. - DOI - PubMed
    1. Peigneur S., Tytgat J. Toxins in Drug Discovery and Pharmacology. Toxins. 2018;10:126. doi: 10.3390/toxins10030126. - DOI - PMC - PubMed
    1. Soares S.C., Lindstrom B., Esteves F., Ohman A. The Hidden Snake in the Grass: Superior Detection of Snakes in Challenging Attentional Conditions. PLoS ONE. 2014;9:e114724. doi: 10.1371/journal.pone.0114724. - DOI - PMC - PubMed
    1. Isbell L.A. Snakes as agents of evolutionary change in primate brains. J. Hum. Evol. 2006;51:1–35. doi: 10.1016/j.jhevol.2005.12.012. - DOI - PubMed
    1. Casewell N.R., Wuster W., Vonk F.J., Harrison R.A., Fry B.G. Complex cocktails: The evolutionary novelty of venoms. Trends Ecol. Evol. 2013;28:219–229. doi: 10.1016/j.tree.2012.10.020. - DOI - PubMed

Publication types

MeSH terms

Substances