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Naja nigricollis three-finger toxins (3FTxs) are a major class of non-enzymatic proteins found in the venom of the black-necked spitting cobra, characterized by a structural motif of three beta-stranded loops extending from a central core [1]. These toxins primarily function as potent neurotoxins that target the postsynaptic nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction [2]. By binding to these receptors with high affinity, they competitively inhibit acetylcholine, leading to muscle paralysis and potentially fatal respiratory failure [3]. Beyond neurotoxicity, the 3FTx family in N. nigricollis includes cytotoxins (or cardiotoxins) that cause significant local tissue damage and necrosis by disrupting cell membrane integrity [4]. These cytotoxins are particularly relevant to the spitting behavior of this species, as they contribute to ophthalmic damage when venom is sprayed into the eyes [5]. In clinical medicine, these toxins are the primary targets for neutralization by antivenoms, which contain antibodies designed to bind and sequester the toxins before they reach their physiological targets [6]. They also serve as critical templates for researching synthetic inhibitors and understanding cholinergic signaling in the nervous system [7].
Competitive antagonism of postsynaptic nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction and direct disruption of cell membranes via pore formation.
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