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 and Bin Wu ()
Additional contact information
Qin Gong: Nanyang Technological University
Ziqi Long: Nanyang Technological University
Franklin L. Zhong: Institute of Medical Biology, A*STAR
Daniel Eng Thiam Teo: Institute of Medical Biology, A*STAR
Yibo Jin: Nanyang Technological University
Zhan Yin: Nanyang Technological University
Zhao Zhi Boo: Nanyang Technological University
Yaming Zhang: Nanyang Technological University
Jiawen Zhang: Nanyang Technological University
Renliang Yang: Nanyang Technological University
Shashi Bhushan: Nanyang Technological University
Bruno Reversade: Institute of Medical Biology, A*STAR
Zongli Li: Harvard Medical School
Bin Wu: Nanyang Technological University

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07447-9

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DOI: 10.1038/s41467-018-07447-9

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