Two Epitope Regions Revealed in the Complex of IL-17A and Anti-IL-17A V<sub>H</sub>H Domain
Interleukin-17 (IL-17) is a cytokine produced by the Th17 cells. It is involved in chronic inflammation in patients with autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis. The antibodies targeting IL-17 and/or IL-17R are therapy tools...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/23/14904 |
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| author | Olga Kostareva Arina Svoeglazova Ilya Kolyadenko Alexey Nikulin Stanislav Evdokimov Uliana Dzhus Azat Gabdulkhakov Svetlana Tishchenko |
| author_facet | Olga Kostareva Arina Svoeglazova Ilya Kolyadenko Alexey Nikulin Stanislav Evdokimov Uliana Dzhus Azat Gabdulkhakov Svetlana Tishchenko |
| author_sort | Olga Kostareva |
| collection | DOAJ |
| description | Interleukin-17 (IL-17) is a cytokine produced by the Th17 cells. It is involved in chronic inflammation in patients with autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis. The antibodies targeting IL-17 and/or IL-17R are therapy tools for these diseases. Netakimab is an IL-17A-specific antibody containing a <i>Lama glama</i> V<sub>H</sub>H derivative domain and a VL variable domain. We have determined the crystal structure of the IL-17A-specific V<sub>H</sub>H domain in complex with IL-17A at 2.85 Å resolution. Certain amino acid residues of the three complementary-determining regions of the V<sub>H</sub>H domain form a network of solvent-inaccessible hydrogen bonds with two epitope regions of IL-17A. The β-turn of IL-17A, which forms the so-called epitope-1, appears to be the main region of IL-17A interaction with the antibody. Contacts formed by the IL-17A mobile C-terminal region residues (epitope-2) further stabilize the antibody–antigen complex. |
| first_indexed | 2024-03-09T17:45:53Z |
| format | Article |
| id | doaj.art-d2724b90e44c4ed495bbc5e7d6236209 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T17:45:53Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d2724b90e44c4ed495bbc5e7d62362092023-11-24T11:09:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123231490410.3390/ijms232314904Two Epitope Regions Revealed in the Complex of IL-17A and Anti-IL-17A V<sub>H</sub>H DomainOlga Kostareva0Arina Svoeglazova1Ilya Kolyadenko2Alexey Nikulin3Stanislav Evdokimov4Uliana Dzhus5Azat Gabdulkhakov6Svetlana Tishchenko7Institute of Protein Research, Russian Academy of Sciences, Institutskaya, 4, 142290 Pushchino, RussiaInstitute of Protein Research, Russian Academy of Sciences, Institutskaya, 4, 142290 Pushchino, RussiaInstitute of Protein Research, Russian Academy of Sciences, Institutskaya, 4, 142290 Pushchino, RussiaInstitute of Protein Research, Russian Academy of Sciences, Institutskaya, 4, 142290 Pushchino, RussiaCJSC Biocad, ul.Svyazi., 34-A, sett. Strelna, 198515 Saint-Petersburg, RussiaInstitute of Protein Research, Russian Academy of Sciences, Institutskaya, 4, 142290 Pushchino, RussiaInstitute of Protein Research, Russian Academy of Sciences, Institutskaya, 4, 142290 Pushchino, RussiaInstitute of Protein Research, Russian Academy of Sciences, Institutskaya, 4, 142290 Pushchino, RussiaInterleukin-17 (IL-17) is a cytokine produced by the Th17 cells. It is involved in chronic inflammation in patients with autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis. The antibodies targeting IL-17 and/or IL-17R are therapy tools for these diseases. Netakimab is an IL-17A-specific antibody containing a <i>Lama glama</i> V<sub>H</sub>H derivative domain and a VL variable domain. We have determined the crystal structure of the IL-17A-specific V<sub>H</sub>H domain in complex with IL-17A at 2.85 Å resolution. Certain amino acid residues of the three complementary-determining regions of the V<sub>H</sub>H domain form a network of solvent-inaccessible hydrogen bonds with two epitope regions of IL-17A. The β-turn of IL-17A, which forms the so-called epitope-1, appears to be the main region of IL-17A interaction with the antibody. Contacts formed by the IL-17A mobile C-terminal region residues (epitope-2) further stabilize the antibody–antigen complex.https://www.mdpi.com/1422-0067/23/23/14904interleukin 17A in complex with V<sub>H</sub>H domainnetakimabcrystal structure |
| spellingShingle | Olga Kostareva Arina Svoeglazova Ilya Kolyadenko Alexey Nikulin Stanislav Evdokimov Uliana Dzhus Azat Gabdulkhakov Svetlana Tishchenko Two Epitope Regions Revealed in the Complex of IL-17A and Anti-IL-17A V<sub>H</sub>H Domain International Journal of Molecular Sciences interleukin 17A in complex with V<sub>H</sub>H domain netakimab crystal structure |
| title | Two Epitope Regions Revealed in the Complex of IL-17A and Anti-IL-17A V<sub>H</sub>H Domain |
| title_full | Two Epitope Regions Revealed in the Complex of IL-17A and Anti-IL-17A V<sub>H</sub>H Domain |
| title_fullStr | Two Epitope Regions Revealed in the Complex of IL-17A and Anti-IL-17A V<sub>H</sub>H Domain |
| title_full_unstemmed | Two Epitope Regions Revealed in the Complex of IL-17A and Anti-IL-17A V<sub>H</sub>H Domain |
| title_short | Two Epitope Regions Revealed in the Complex of IL-17A and Anti-IL-17A V<sub>H</sub>H Domain |
| title_sort | two epitope regions revealed in the complex of il 17a and anti il 17a v sub h sub h domain |
| topic | interleukin 17A in complex with V<sub>H</sub>H domain netakimab crystal structure |
| url | https://www.mdpi.com/1422-0067/23/23/14904 |
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