Please use this identifier to cite or link to this item:
Title: Structural basis of RIP2 activation and signaling
Authors: 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
Keywords: adaptor protein
beta actin
caspase recruitment domain protein 15
caspase recruitment domain protein 4
caspase recruitment domain signaling protein
mitochondria antiviral signaling protein
nlrc4 protein
receptor interacting protein serine threonine kinase 2
snap protein
unclassified drug
protein binding
receptor interacting protein serine threonine kinase 2
recombinant protein
RIPK2 protein, human
bacterial disease
chemical binding
molecular analysis
caspase activation and recruitment domain
cell organelle
controlled study
electron tomography
enzyme activation
enzyme activity
in vitro study
protein protein interaction
signal transduction
site directed mutagenesis
amino acid sequence
cryoelectron microscopy
HEK293 cell line
molecular model
protein domain
protein multimerization
structure activity relation
Bacteria (microorganisms)
Amino Acid Sequence
CARD Signaling Adaptor Proteins
Cryoelectron Microscopy
HEK293 Cells
Models, Molecular
Protein Binding
Protein Domains
Protein Multimerization
Receptor-Interacting Protein Serine-Threonine Kinase 2
Recombinant Proteins
Signal Transduction
Structure-Activity Relationship
Issue Date: 2018
Publisher: Nature Publishing Group
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 (2018). Structural basis of RIP2 activation and signaling. Nature Communications 9 (1) : 4993. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
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. © 2018, The Author(s).
Source Title: Nature Communications
ISSN: 2041-1723
DOI: 10.1038/s41467-018-07447-9
Rights: Attribution 4.0 International
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1038_s41467-018-07447-9.pdf3.09 MBAdobe PDF



Google ScholarTM



This item is licensed under a Creative Commons License Creative Commons