Pore-Forming Proteins from Cnidarians and Arachnids as Potential Biotechnological Tools

Abstract

Animal venoms are complex mixtures of highly specialized toxic molecules. Cnidarians and arachnids produce pore-forming proteins (PFPs) directed against the plasma membrane of their target cells. Among PFPs from cnidarians, actinoporins stand out for their small size and molecular simplicity. While native actinoporins require only sphingomyelin for membrane binding, engineered chimeras containing a recognition antibody-derived domain fused to an actinoporin isoform can nonetheless serve as highly specific immunotoxins. Examples of such constructs targeted against malignant cells have been already reported. However, PFPs from arachnid venoms are less well-studied from a structural and functional point of view. Spiders from the Latrodectus genus are professional insect hunters that, as part of their toxic arsenal, produce large PFPs known as latrotoxins. Interestingly, some latrotoxins have been identified as potent and highly-specific insecticides. Given the proteinaceous nature of these toxins, their promising future use as efficient bioinsecticides is discussed throughout this Perspective. Protein engineering and large-scale recombinant production are critical steps for the use of these PFPs as tools to control agriculturally important insect pests. In summary, both families of PFPs, from Cnidaria and Arachnida, appear to be molecules with promising biotechnological applications.

Investigation of the structure‐activity relationship in ponericin L1 from Neoponera goeldii

“…[ 3‐5 ] Nonetheless, when isolated, the individual components can have significant potential as therapeutic agents. [ 6‐9 ] Notably, a number of commercially available drugs such as captopril, eptifibatide, tirofiban, ziconotide, and exenatide all have origins in venoms from a variety of organisms. [ 2 ]…”

Inclusion of a Furin Cleavage Site Enhances Antitumor Efficacy against Colorectal Cancer Cells of Ribotoxin α-Sarcin- or RNase T1-Based Immunotoxins

“…Toxins from different origins, have also been employed such as Pseudomonas exotoxin A, Diphteria toxin, actinoporins, gelonin, and the plant toxin ricin, among others [17,18,19,20,21,22,23,24,25,26]. Interestingly, ribonucleases (RNases) have acquired a significant importance due to their ideal features for being included as immunotoxin toxic domains [27,28,29,30,31,32].…”

Functional and Structural Variation among Sticholysins, Pore-Forming Proteins from the Sea Anemone Stichodactyla helianthus

“…Another type of membrane-targeting toxin frequently appearing in venoms does not affect its protein constituents but directly the integrity of the whole structure, maintained mostly by phospholipids. This is the case of the aforementioned phospholipases or the widespread pore-forming proteins (PFPs) [ 12 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Given the critical importance of the plasma membrane for cell viability, its disruption usually has fatal consequences that, in many cases, imply cell death by osmotic shock.…”

“…PFPs are a group of toxins whose activity precisely relies on the disruption of the lipid membranes by forming pores. These kinds of toxins escape to the archetypal biochemical classification that sorts proteins into water-soluble or membrane macromolecules [ 12 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 34 , 35 , 36 , 37 ]. They are produced as soluble monomeric proteins and remain stably folded and water-soluble but, upon interaction with a membrane receptor in the target cell, undergo a molecular metamorphosis to become an oligomeric transmembrane assemble, that forms a pore within the membrane core.…”