Rational attenuation of elapid long-chain neurotoxin by targeted residue substitution and disulfide architecture simplification: implications for receptor interaction and immune recognition
Rational attenuation of elapid long-chain neurotoxin by targeted residue substitution and disulfide architecture simplification: implications for receptor interaction and immune recognition
Rational attenuation of elapid long-chain neurotoxin by targeted residue substitution and disulfide architecture simplification: implications for receptor interaction and immune recognition Abstract Elapid long-chain neurotoxins (LNTxs) exert their toxicity through high-affinity binding to nicotinic acetylcholine receptors (nAChRs). Specific residues mediate this process, including basic (Lys23, Arg33, Arg36, Lys49), structural (Cys26, Cys30), and aromatic (Phe29) amino acids. To investigate the functional and immunogenic implications of modifying these residues, we designed two recombinant variants of a consensus LNTx. The first variant, rLcNTx V1, contains charge-reversal mutations at four key basic positions, while the second, rLcNTx V2, lacks the segment corresponding to the fifth disulfide bond. We expressed both variants in Escherichia coli Origami cells. rLcNTx V1 was recovered in a soluble form, but rLcNTx V2 was present only in inclusion bodies. We assessed the binding ...
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