QTY code-designed water-soluble Fc-fusion cytokine receptors bind to their respective ligands
Cytokine release syndrome (CRS), or "cytokine storm," is the leading side effect during CAR-T therapy that is potentially life-threatening. It also plays a critical role in viral infections such as COVID-19. Therefore, efficient removal of excessive cytokines is essential for treatment. We...
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| Format: | Article |
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2020
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| Online Access: | https://hdl.handle.net/1721.1/125601 |
| _version_ | 1826210616621137920 |
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| author | Hao, Shilei Jin, David Zhang, Shuguang Qing, Rui |
| author2 | Massachusetts Institute of Technology. Media Laboratory |
| author_facet | Massachusetts Institute of Technology. Media Laboratory Hao, Shilei Jin, David Zhang, Shuguang Qing, Rui |
| author_sort | Hao, Shilei |
| collection | MIT |
| description | Cytokine release syndrome (CRS), or "cytokine storm," is the leading side effect during CAR-T therapy that is potentially life-threatening. It also plays a critical role in viral infections such as COVID-19. Therefore, efficient removal of excessive cytokines is essential for treatment. We previously reported a novel protein modification tool called the QTY code, through which hydrophobic amino acids Leu, Ile, Val and Phe are replaced by Gln (Q), Thr (T) and Tyr (Y). Thus the functional detergent-free equivalents of membrane proteins can be designed. Here we report the application of the QTY code on six variants of cytokine receptors, including interleukin receptors IL4R and IL10R, chemokine receptors CCR9 and CXCR2, as well as interferon receptors IFNγR1 and IFNλR1. QTYvariant cytokine receptors exhibit physiological properties similar to those of native receptors without the presence of hydrophobic segments. The receptors were fused to the Fc region of IgG protein to form an antibody-like structure. These QTY code-designed Fc fusion receptors were expressed in E. coli and purified. The resulting water-soluble fusion receptors bind to their respective ligands with Kd values affinity similar to isolated native receptors. Our cytokine receptor-Fc fusion proteins potentially serve as an antibody-like decoy to dampen the excessive cytokine levels associated with CRS and COVID-19 infection. Keywords: cytokine release syndrome, protein design, water-soluble membrane protein, antibody-like fusion protein |
| first_indexed | 2024-09-23T14:52:47Z |
| format | Article |
| id | mit-1721.1/125601 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T14:52:47Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | mit-1721.1/1256012022-10-01T23:07:02Z QTY code-designed water-soluble Fc-fusion cytokine receptors bind to their respective ligands Hao, Shilei Jin, David Zhang, Shuguang Qing, Rui Massachusetts Institute of Technology. Media Laboratory Koch Institute for Integrative Cancer Research at MIT Cytokine release syndrome (CRS), or "cytokine storm," is the leading side effect during CAR-T therapy that is potentially life-threatening. It also plays a critical role in viral infections such as COVID-19. Therefore, efficient removal of excessive cytokines is essential for treatment. We previously reported a novel protein modification tool called the QTY code, through which hydrophobic amino acids Leu, Ile, Val and Phe are replaced by Gln (Q), Thr (T) and Tyr (Y). Thus the functional detergent-free equivalents of membrane proteins can be designed. Here we report the application of the QTY code on six variants of cytokine receptors, including interleukin receptors IL4R and IL10R, chemokine receptors CCR9 and CXCR2, as well as interferon receptors IFNγR1 and IFNλR1. QTYvariant cytokine receptors exhibit physiological properties similar to those of native receptors without the presence of hydrophobic segments. The receptors were fused to the Fc region of IgG protein to form an antibody-like structure. These QTY code-designed Fc fusion receptors were expressed in E. coli and purified. The resulting water-soluble fusion receptors bind to their respective ligands with Kd values affinity similar to isolated native receptors. Our cytokine receptor-Fc fusion proteins potentially serve as an antibody-like decoy to dampen the excessive cytokine levels associated with CRS and COVID-19 infection. Keywords: cytokine release syndrome, protein design, water-soluble membrane protein, antibody-like fusion protein China Scholarship Council (grant no. 201808505038) 2020-06-01T21:02:43Z 2020-06-01T21:02:43Z 2020-04 Article http://purl.org/eprint/type/JournalArticle 2633-2892 https://hdl.handle.net/1721.1/125601 Hao, Shilei, et al., "QTY code-designed water-soluble Fc-fusion cytokine receptors bind to their respective ligands." QRB Discovery (Apr. 2020): doi 10.1017/qrd.2020.4 ©2020 Author(s) 10.1017/qrd.2020.4 QRB Discovery Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Cambridge University Press |
| spellingShingle | Hao, Shilei Jin, David Zhang, Shuguang Qing, Rui QTY code-designed water-soluble Fc-fusion cytokine receptors bind to their respective ligands |
| title | QTY code-designed water-soluble Fc-fusion cytokine receptors bind to their respective ligands |
| title_full | QTY code-designed water-soluble Fc-fusion cytokine receptors bind to their respective ligands |
| title_fullStr | QTY code-designed water-soluble Fc-fusion cytokine receptors bind to their respective ligands |
| title_full_unstemmed | QTY code-designed water-soluble Fc-fusion cytokine receptors bind to their respective ligands |
| title_short | QTY code-designed water-soluble Fc-fusion cytokine receptors bind to their respective ligands |
| title_sort | qty code designed water soluble fc fusion cytokine receptors bind to their respective ligands |
| url | https://hdl.handle.net/1721.1/125601 |
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