5YRN

Structure of RIP2 CARD domain

Summary for 5YRN

• Entry DOI: 10.2210/pdb5yrn/pdb
• EMDB information: 6663 6842
• Descriptor: Receptor-interacting serine/threonine-protein kinase 2 (1 entity in total)
• Functional Keywords: innate immune signaling complex, immune system, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 12
• Total formula weight: 151457.26

Authors

Wu, B.,Gong, Q. (deposition date: 2017-11-09, release date: 2018-11-14, Last modification date: 2024-03-27)

Primary citation

Gong, Q.,Long, Z.,Zhong, F.L.,Teo, D.E.T.,Jin, Y.,Yin, Z.,Boo, Z.Z.,Zhang, Y.,Zhang, J.,Yang, R.,Bhushan, S.,Reversade, B.,Li, Z.,Wu, B.
Structural basis of RIP2 activation and signaling.
Nat Commun, 9:4993-4993, 2018

PubMed 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.

PubMed: 30478312
DOI: 10.1038/s41467-018-07447-9

Experimental method

ELECTRON MICROSCOPY (4.1 Å)