Structural basis of RIP2 activation and signaling
| العنوان: | Structural basis of RIP2 activation and signaling |
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| المؤلفون: | Franklin L. Zhong, Bruno Reversade, Daniel Eng Thiam Teo, Yibo Jin, Qin Gong, Jiawen Zhang, Zhan Yin, Bin Wu, Zongli Li, Yaming Zhang, Zhao Zhi Boo, Renliang Yang, Long Ziqi, Shashi Bhushan |
| المساهمون: | Center for Reproductive Medicine, ACS - Diabetes & metabolism, ARD - Amsterdam Reproduction and Development, ACS - Heart failure & arrhythmias, Reversade, Bruno, 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, Li, Zongli, Wu, Bin, School of Medicine, Department of Histology and Embryology, School of Biological Sciences, Institute of Structural Biology |
| المصدر: | Nature Communications, Vol 9, Iss 1, Pp 1-13 (2018) Nature communications, 9(1):4993. Nature Publishing Group Nature Communications |
| بيانات النشر: | Nature Publishing Group, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Models, Molecular, 0301 basic medicine, Science, Protein domain, General Physics and Astronomy, Mutagenesis (molecular biology technique), Plasma protein binding, Article, General Biochemistry, Genetics and Molecular Biology, RIPK2, Structure-Activity Relationship, 03 medical and health sciences, Protein Domains, Receptor-Interacting Protein Serine-Threonine Kinase 2, NOD1, Humans, Amino Acid Sequence, lcsh:Science, Science and technology, Receptor-interacting protein-2, Helical reconstruction, Kinase-activity, Crohns-disease, Cell-death, Innate, Inflammasome, Domain, ASC, Multidisciplinary, Chemistry, Cryoelectron Microscopy, HEK 293 cells, Signal transducing adaptor protein, General Chemistry, Recombinant Proteins, Science::Biological sciences [DRNTU], Cell biology, CARD Signaling Adaptor Proteins, body regions, HEK293 Cells, 030104 developmental biology, lcsh:Q, Protein Multimerization, Signal transduction, Protein Binding, Signal Transduction |
| الوصف: | 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. The pathogen recognition receptors NOD1/2 recognize bacterial cell wall components and signal through their downstream adapter kinase RIP2 via a CARD (Caspase activation and recruitment domain) mediated oligomerization process. Here the authors present the cryo-EM structure of the active RIP2-CARD filament and discuss implications for NOD1/2-RIP2 signalling. |
| وصف الملف: | pdf; application/pdf |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd24949892b6b033045e393783224eb9Test http://link.springer.com/article/10.1038/s41467-018-07447-9Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dd24949892b6b033045e393783224eb9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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