Three-Finger Toxins from Brazilian Coral Snakes: From Molecular Framework to Insights in Biological Function

Abstract

Studies on 3FTxs around the world are showing the amazing diversity in these proteins both in structure and function. In Brazil, we have not realized the broad variety of their amino acid sequences and probable diversified structures and targets. In this context, this work aims to conduct an in silico systematic study on available 3FTxs found in Micrurus species from Brazil. We elaborated a specific guideline for this toxin family. First, we grouped them according to their structural homologue predicted by HHPred server and further curated manually. For each group, we selected one sequence and constructed a representative structural model. By looking at conserved features and comparing with the information available in the literature for this toxin family, we managed to point to potential biological functions. In parallel, the phylogenetic relationship was estimated for our database by maximum likelihood analyses and a phylogenetic tree was constructed including the homologous 3FTx previously characterized. Our results highlighted an astonishing diversity inside this family of toxins, showing some groups with expected functional similarities to known 3FTxs, and pointing out others with potential novel roles and perhaps structures. Moreover, this classification guideline may be useful to aid future studies on these abundant toxins.

A current perspective on snake venom composition and constituent protein families

“…VEGFs are most common in true vipers, being present in 77% of species (mean abundance 3%), then pit vipers, 42% of species (mean abundance 1.5%), and only 13% of elapids (mean abundance 0.06%) (Table 3). They have been recorded as being 25 kDa homodimeric heparin-binding proteins (Ferreira et al 2021), but one toxin isolated from a pit viper was heterodimeric with a molecular mass of 37 kDa (monomeric masses of 13 and 26 kDa) (Nakamura et al 2014).…”

“…The study of snake venom is a multi-disciplinary endeavour encompassing a diverse range of research areas from the therapeutic potential of toxins and drug discovery (Kalita et al 2021;Li et al 2018;Omidi et al 2021; Urra and Araya-Maturana 2022), antivenom development and the treatment of snakebite (de Silva et al 2016b, c, d, a;Fry et al 2003;Gutiérrez et al 2011;Harrison et al 2011;Maduwage et al 2015;Visser et al 2008), pathophysiology of envenomation (Maduwage et al 2013;Mamede et al 2020;Silva et al 2016bSilva et al , 2016c, using toxins as physiological probes to better understand physiological mechanisms (Chiappinelli 1983;Harvey and Robertson 2005;Kerns et al 1999;Wijeyewickrema et al 2005;Yang et al 2016), and venom characterisation, which includes venom composition and the sequence, structure and pharmacology of toxins (Bolt 2021;Kleiz-Ferreira et al 2021;Tasoulis et al 2022b;Yang et al 2016). More recently the evolutionary biology of toxins and venom has been investigated, including both inter-and intraspecific venom variation and its evolutionary and ecological significance (Margres et al 2021;Mora-Obando et al 2020;Rautsaw et al 2019;Zancolli et al 2019).…”

The Cloning and Characterization of a Three-Finger Toxin Homolog (NXH8) from the Coralsnake Micrurus corallinus That Interacts with Skeletal Muscle Nicotinic Acetylcholine Receptors

“…Compared to the extensive knowledge available for members of the 3FTx family in elapids in general, considerably less is known of the 3FTx of Micrurus spp., primarily because of the difficulty in obtaining venom for toxin purification. As of October 2023, a PubMed search using terms such as “ Micrurus three-finger toxin” yielded only 42 studies, many of which focused on in silico analyses of transcriptomic and proteomic data, with few actually dealing with the biological and pharmacological characterization of these toxins; nevertheless, some reports have described the partial or complete characterization of short α-neurotoxins and phospholipases A 2 [ 7 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ].…”

Pharmacological Screening of Venoms from Five Brazilian Micrurus Species on Different Ion Channels

“…This protein diversity probably leads to different biological activities that contribute to the envenomation outcome. We know for the 3FTxs, for example, that we can find a range of toxins with different functions depending on the protein sequence and local structures [3,16]. Importantly, despite the diversified toxins that we can find in Brazilian Micrurus species [8,16], currently few proteins were explored and characterized in terms of their structures and functions [17][18][19][20].…”