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TitleStructural basis of RIP2 activation and signaling.
Journal, issue, pagesNat Commun, Vol. 9, Issue 1, Page 4993, Year 2018
Publish dateNov 26, 2018
AuthorsQin Gong / Ziqi Long / Franklin L Zhong / Daniel Eng Thiam Teo / Yibo Jin / Zhan Yin / Zhao Zhi Boo / Yaming Zhang / Jiawen Zhang / Renliang Yang / Shashi Bhushan / Bruno Reversade / Zongli Li / Bin Wu /
PubMed 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- ...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.
External linksNat Commun / PubMed:30478312 / PubMed Central
MethodsEM (helical sym.)
Resolution4.1 - 4.85 Å
Structure data

EMDB-6663:
Structure of RIP2 CARD domain
Method: EM (helical sym.) / Resolution: 4.85 Å

6842

5yrn

EMDB-6842, PDB-5yrn:
Structure of RIP2 CARD domain
Method: EM (helical sym.) / Resolution: 4.1 Å

Source
  • homo sapiens (human)
KeywordsTRANSFERASE / Innate Immune signaling complex / IMMUNE SYSTEM

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