Alanine Mutagenesis Identifies Specific Amino Acids of Nemertide Alpha-1 Activity and Its Binding to Target Receptors.

ABSTRACT: We recently discovered and characterized a novel family of peptide toxins, the alpha-nemertides, from the marine ribbon worm Lineus longissimus. These 31-residue peptides show potent neurotoxicity against invertebrate voltage-gated sodium (Na_v) channels, making them promising candidates for biopesticide development. To explore structure-activity relationships, we synthesized 20 nemertide alpha-1 mutants (17 alanine, 3 lysine substitutions) to identify residues critical for activity and selectivity. Key positions, including S12, T17, N19, W22, and F24, were found to influence activity on Na_v channels significantly. Notably, the S12A mutant showed high selectivity for invertebrate Na_vs, suggesting its potential as a selective tool or lead scaffold. Our

SUBMITTER: Laborde Q 

PROVIDER: S-EPMC12836348 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature