Structural basis of RIP2 activation and signaling
Signals arising from bacterial infections are detected by pathogen recognition receptors (PRRs) and are transduced by specialized adapter proteins in mammalian cells. The Receptor-interacting-serine/threonine-protein kinase 2 (RIPK2 or RIP2) is such an adapter protein that is critical for signal pro...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2019
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| Online Access: | https://hdl.handle.net/10356/89110 http://hdl.handle.net/10220/47668 |
| _version_ | 1826129887436472320 |
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| author | Gong, Qin Long, Ziqi Zhong, Franklin L. Teo, Daniel Eng Thiam Jin, Yibo Yin, Zhan Boo, Zhao Zhi Zhang, Yaming Zhang, Jiawen Yang, Renliang Bhushan, Shashi Reversade, Bruno Li, Zongli Wu, Bin |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Gong, Qin Long, Ziqi Zhong, Franklin L. Teo, Daniel Eng Thiam Jin, Yibo Yin, Zhan Boo, Zhao Zhi Zhang, Yaming Zhang, Jiawen Yang, Renliang Bhushan, Shashi Reversade, Bruno Li, Zongli Wu, Bin |
| author_sort | Gong, Qin |
| collection | NTU |
| description | Signals arising from bacterial infections are detected by pathogen recognition receptors (PRRs) and are transduced by specialized adapter proteins in mammalian cells. The Receptor-interacting-serine/threonine-protein kinase 2 (RIPK2 or RIP2) is such an adapter protein that is critical for signal propagation of the Nucleotide-binding-oligomerization-domain-containing proteins 1/2 (NOD1 and NOD2). Dysregulation of this signaling pathway leads to defects in bacterial detection and in some cases autoimmune diseases. Here, we show that the Caspase-activation-and-recruitment-domain (CARD) of RIP2 (RIP2-CARD) forms oligomeric structures upon stimulation by either NOD1-CARD or NOD2-2CARD. We reconstitute this complex, termed the RIPosome in vitro and solve the cryo-EM filament structure of the active RIP2-CARD complex at 4.1 Å resolution. The structure suggests potential mechanisms by which CARD domains from NOD1 and NOD2 initiate the oligomerization process of RIP2-CARD. Together with structure guided mutagenesis experiments at the CARD-CARD interfaces, we demonstrate molecular mechanisms how RIP2 is activated and self-propagating such signal. |
| first_indexed | 2024-10-01T07:47:32Z |
| format | Journal Article |
| id | ntu-10356/89110 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T07:47:32Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/891102023-02-28T17:02:28Z Structural basis of RIP2 activation and signaling Gong, Qin Long, Ziqi Zhong, Franklin L. Teo, Daniel Eng Thiam Jin, Yibo Yin, Zhan Boo, Zhao Zhi Zhang, Yaming Zhang, Jiawen Yang, Renliang Bhushan, Shashi Reversade, Bruno Li, Zongli Wu, Bin School of Biological Sciences Institute of Structural Biology DRNTU::Science::Biological sciences Signals arising from bacterial infections are detected by pathogen recognition receptors (PRRs) and are transduced by specialized adapter proteins in mammalian cells. The Receptor-interacting-serine/threonine-protein kinase 2 (RIPK2 or RIP2) is such an adapter protein that is critical for signal propagation of the Nucleotide-binding-oligomerization-domain-containing proteins 1/2 (NOD1 and NOD2). Dysregulation of this signaling pathway leads to defects in bacterial detection and in some cases autoimmune diseases. Here, we show that the Caspase-activation-and-recruitment-domain (CARD) of RIP2 (RIP2-CARD) forms oligomeric structures upon stimulation by either NOD1-CARD or NOD2-2CARD. We reconstitute this complex, termed the RIPosome in vitro and solve the cryo-EM filament structure of the active RIP2-CARD complex at 4.1 Å resolution. The structure suggests potential mechanisms by which CARD domains from NOD1 and NOD2 initiate the oligomerization process of RIP2-CARD. Together with structure guided mutagenesis experiments at the CARD-CARD interfaces, we demonstrate molecular mechanisms how RIP2 is activated and self-propagating such signal. MOE (Min. of Education, S’pore) Published version 2019-02-14T06:57:36Z 2019-12-06T17:18:04Z 2019-02-14T06:57:36Z 2019-12-06T17:18:04Z 2018 Journal Article Gong, Q., Long, Z., Zhong, F. L., Teo, D. E. T., Jin, Y., Yin, Z., . . . Wu, B. (2018). Structural basis of RIP2 activation and signaling. Nature Communications, 9(1), 4993-. doi:10.1038/s41467-018-07447-9 https://hdl.handle.net/10356/89110 http://hdl.handle.net/10220/47668 10.1038/s41467-018-07447-9 en Nature Communications © 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 13 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Gong, Qin Long, Ziqi Zhong, Franklin L. Teo, Daniel Eng Thiam Jin, Yibo Yin, Zhan Boo, Zhao Zhi Zhang, Yaming Zhang, Jiawen Yang, Renliang Bhushan, Shashi Reversade, Bruno Li, Zongli Wu, Bin Structural basis of RIP2 activation and signaling |
| title | Structural basis of RIP2 activation and signaling |
| title_full | Structural basis of RIP2 activation and signaling |
| title_fullStr | Structural basis of RIP2 activation and signaling |
| title_full_unstemmed | Structural basis of RIP2 activation and signaling |
| title_short | Structural basis of RIP2 activation and signaling |
| title_sort | structural basis of rip2 activation and signaling |
| topic | DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/89110 http://hdl.handle.net/10220/47668 |
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