Comparative Structural and Biophysical Investigation of <i>Lycosa erythrognatha</i> Toxin I (LyeTx I) and Its Analog LyeTx I-b
<b>Background/Objectives:</b> This study investigates the structural and biophysical properties of the wild-type antimicrobial peptide LyeTx I, isolated from the venom of the spider <i>Lycosa erythrognatha</i>, and its analog LyeTx I-b, designed to enhance antibacterial activ...
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2025-01-01
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| author | Amanda Neves de Souza Gabriele de Azevedo Cardoso Lúcio Otávio Nunes Christopher Aisenbrey Evgeniy Salnikov Kelton Rodrigues de Souza Ahmad Saad Maria Elena de Lima Jarbas Magalhães Resende Burkhard Bechinger Rodrigo Moreira Verly |
| author_facet | Amanda Neves de Souza Gabriele de Azevedo Cardoso Lúcio Otávio Nunes Christopher Aisenbrey Evgeniy Salnikov Kelton Rodrigues de Souza Ahmad Saad Maria Elena de Lima Jarbas Magalhães Resende Burkhard Bechinger Rodrigo Moreira Verly |
| author_sort | Amanda Neves de Souza |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> This study investigates the structural and biophysical properties of the wild-type antimicrobial peptide LyeTx I, isolated from the venom of the spider <i>Lycosa erythrognatha</i>, and its analog LyeTx I-b, designed to enhance antibacterial activity, selectivity, and membrane interactions by the acetylation and increased amphipathicty. <b>Methods</b>: To understand the mechanisms behind these enhanced properties, comparative analyses of the structural, topological, biophysical, and thermodynamic aspects of the interactions between each peptide and phospholipid bilayers were evaluated. Both peptides were isotopically labeled with <sup>2</sup>H<sub>3</sub>-Ala and <sup>15</sup>N-Leu to facilitate structural studies via NMR spectroscopy. <b>Results:</b> Circular dichroism and solid-state NMR analyses revealed that, while both peptides adopt α-helical conformations in membrane mimetic environments, LyeTx I-b exhibits a more amphipathic and extended helical structure, which correlates with its enhanced membrane interaction. The thermodynamic properties of the peptide–membrane interactions were quantitatively evaluated in the presence of phospholipid bilayers using ITC and DSC, highlighting a greater propensity of LyeTx I-b to disrupt lipid vesicles. Calcein release studies reveal that both peptides cause vesicle disruption, although DLS measurements and TEM imaging indicate distinct effects on phospholipid vesicle organization. While LyeTx I-b permeabilizes anionic membrane retaining the vesicle integrity, LyeTx I promotes significant vesicle agglutination. Furthermore, DSC and calcein release assays indicate that LyeTx I-b exhibits significantly lower cytotoxicity toward eukaryotic membranes compared to LyeTx I, suggesting greater selectivity for bacterial membranes. <b>Conclusions</b>: Our findings provide insights into the structural and functional modifications that enhance the antimicrobial and therapeutic potential of LyeTx I-b, offering valuable guidance for the design of novel peptides targeting resistant bacterial infections and cancer. |
| format | Article |
| id | doaj-art-e353007f82ce478e8345d77333062a0b |
| institution | Kabale University |
| issn | 2079-6382 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Antibiotics |
| spelling | doaj-art-e353007f82ce478e8345d77333062a0b2025-01-24T13:18:49ZengMDPI AGAntibiotics2079-63822025-01-011416610.3390/antibiotics14010066Comparative Structural and Biophysical Investigation of <i>Lycosa erythrognatha</i> Toxin I (LyeTx I) and Its Analog LyeTx I-bAmanda Neves de Souza0Gabriele de Azevedo Cardoso1Lúcio Otávio Nunes2Christopher Aisenbrey3Evgeniy Salnikov4Kelton Rodrigues de Souza5Ahmad Saad6Maria Elena de Lima7Jarbas Magalhães Resende8Burkhard Bechinger9Rodrigo Moreira Verly10Departamento de Química, Faculdade de Ciências Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Campus JK, Diamantina 39100-000, MG, BrazilDepartamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, BrazilDepartamento de Química, Faculdade de Ciências Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Campus JK, Diamantina 39100-000, MG, BrazilInstitut de Chimie, Université de Strasbourg, CNRS, UMR7177, 67000 Strasbourg, FranceInstitut de Chimie, Université de Strasbourg, CNRS, UMR7177, 67000 Strasbourg, FranceDepartamento de Química, Faculdade de Ciências Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Campus JK, Diamantina 39100-000, MG, BrazilInstitut de Chimie, Université de Strasbourg, CNRS, UMR7177, 67000 Strasbourg, FrancePrograma de Pós-Graduação Stricto Sensu em Medicina e Biomedicina, Faculdade de Saúde Santa Casa de Belo Horizonte, Belo Horizonte 30150-221, MG, BrazilDepartamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, MG, BrazilInstitut de Chimie, Université de Strasbourg, CNRS, UMR7177, 67000 Strasbourg, FranceDepartamento de Química, Faculdade de Ciências Exatas, Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM), Campus JK, Diamantina 39100-000, MG, Brazil<b>Background/Objectives:</b> This study investigates the structural and biophysical properties of the wild-type antimicrobial peptide LyeTx I, isolated from the venom of the spider <i>Lycosa erythrognatha</i>, and its analog LyeTx I-b, designed to enhance antibacterial activity, selectivity, and membrane interactions by the acetylation and increased amphipathicty. <b>Methods</b>: To understand the mechanisms behind these enhanced properties, comparative analyses of the structural, topological, biophysical, and thermodynamic aspects of the interactions between each peptide and phospholipid bilayers were evaluated. Both peptides were isotopically labeled with <sup>2</sup>H<sub>3</sub>-Ala and <sup>15</sup>N-Leu to facilitate structural studies via NMR spectroscopy. <b>Results:</b> Circular dichroism and solid-state NMR analyses revealed that, while both peptides adopt α-helical conformations in membrane mimetic environments, LyeTx I-b exhibits a more amphipathic and extended helical structure, which correlates with its enhanced membrane interaction. The thermodynamic properties of the peptide–membrane interactions were quantitatively evaluated in the presence of phospholipid bilayers using ITC and DSC, highlighting a greater propensity of LyeTx I-b to disrupt lipid vesicles. Calcein release studies reveal that both peptides cause vesicle disruption, although DLS measurements and TEM imaging indicate distinct effects on phospholipid vesicle organization. While LyeTx I-b permeabilizes anionic membrane retaining the vesicle integrity, LyeTx I promotes significant vesicle agglutination. Furthermore, DSC and calcein release assays indicate that LyeTx I-b exhibits significantly lower cytotoxicity toward eukaryotic membranes compared to LyeTx I, suggesting greater selectivity for bacterial membranes. <b>Conclusions</b>: Our findings provide insights into the structural and functional modifications that enhance the antimicrobial and therapeutic potential of LyeTx I-b, offering valuable guidance for the design of novel peptides targeting resistant bacterial infections and cancer.https://www.mdpi.com/2079-6382/14/1/66antimicrobial activity<i>Lycosa erythrognatha</i> antimicrobial peptidepost-translational modificationpeptide–membrane interaction |
| spellingShingle | Amanda Neves de Souza Gabriele de Azevedo Cardoso Lúcio Otávio Nunes Christopher Aisenbrey Evgeniy Salnikov Kelton Rodrigues de Souza Ahmad Saad Maria Elena de Lima Jarbas Magalhães Resende Burkhard Bechinger Rodrigo Moreira Verly Comparative Structural and Biophysical Investigation of <i>Lycosa erythrognatha</i> Toxin I (LyeTx I) and Its Analog LyeTx I-b Antibiotics antimicrobial activity <i>Lycosa erythrognatha</i> antimicrobial peptide post-translational modification peptide–membrane interaction |
| title | Comparative Structural and Biophysical Investigation of <i>Lycosa erythrognatha</i> Toxin I (LyeTx I) and Its Analog LyeTx I-b |
| title_full | Comparative Structural and Biophysical Investigation of <i>Lycosa erythrognatha</i> Toxin I (LyeTx I) and Its Analog LyeTx I-b |
| title_fullStr | Comparative Structural and Biophysical Investigation of <i>Lycosa erythrognatha</i> Toxin I (LyeTx I) and Its Analog LyeTx I-b |
| title_full_unstemmed | Comparative Structural and Biophysical Investigation of <i>Lycosa erythrognatha</i> Toxin I (LyeTx I) and Its Analog LyeTx I-b |
| title_short | Comparative Structural and Biophysical Investigation of <i>Lycosa erythrognatha</i> Toxin I (LyeTx I) and Its Analog LyeTx I-b |
| title_sort | comparative structural and biophysical investigation of i lycosa erythrognatha i toxin i lyetx i and its analog lyetx i b |
| topic | antimicrobial activity <i>Lycosa erythrognatha</i> antimicrobial peptide post-translational modification peptide–membrane interaction |
| url | https://www.mdpi.com/2079-6382/14/1/66 |
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