dc.contributor.authorGong, Qin
dc.contributor.authorLong, Ziqi
dc.contributor.authorZhong, Franklin L.
dc.contributor.authorTeo, Daniel Eng Thiam
dc.contributor.authorJin, Yibo
dc.contributor.authorYin, Zhan
dc.contributor.authorBoo, Zhao Zhi
dc.contributor.authorZhang, Yaming
dc.contributor.authorZhang, Jiawen
dc.contributor.authorYang, Renliang
dc.contributor.authorBhushan, Shashi
dc.contributor.authorReversade, Bruno
dc.contributor.authorLi, Zongli
dc.contributor.authorWu, Bin
dc.date.accessioned2019-02-14T06:57:36Z
dc.date.available2019-02-14T06:57:36Z
dc.date.issued2018
dc.identifier.citationGong, 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/s41467-018-07447-9en_US
dc.identifier.urihttp://hdl.handle.net/10220/47668
dc.description.abstractSignals 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.en_US
dc.description.sponsorshipMOE (Min. of Education, S’pore)en_US
dc.format.extent13 p.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesNature Communicationsen_US
dc.rights© 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/.en_US
dc.subjectDRNTU::Science::Biological sciencesen_US
dc.titleStructural basis of RIP2 activation and signalingen_US
dc.typeJournal Article
dc.contributor.researchInstitute of Structural Biologyen_US
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.identifier.doihttp://dx.doi.org/10.1038/s41467-018-07447-9
dc.description.versionPublished versionen_US


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