Structural basis of RIP2 activation and signaling

Qin 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

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

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.
Original languageEnglish (US)
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Chemistry
  • General Physics and Astronomy

Fingerprint

Dive into the research topics of 'Structural basis of RIP2 activation and signaling'. Together they form a unique fingerprint.

Cite this