6nw2

Structure of human RIPK1 kinase domain in complex with compound 11

Structural highlights

6nw2 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	L4Y
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RIPK1_HUMAN Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex.^[1] ^[2] ^[3]

References

↑ Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B, Tschopp J. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 2000 Dec;1(6):489-95. PMID:11101870 doi:10.1038/82732
↑ Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009 Jun 12;137(6):1112-23. doi: 10.1016/j.cell.2009.05.037. PMID:19524513 doi:10.1016/j.cell.2009.05.037
↑ He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 2009 Jun 12;137(6):1100-11. doi: 10.1016/j.cell.2009.05.021. PMID:19524512 doi:10.1016/j.cell.2009.05.021

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OCA

[1] Holler N, Zaru R, Micheau O, Thome M, Attinger A, Valitutti S, Bodmer JL, Schneider P, Seed B, Tschopp J. Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol. 2000 Dec;1(6):489-95. PMID:11101870 doi:10.1038/82732

[2] Cho YS, Challa S, Moquin D, Genga R, Ray TD, Guildford M, Chan FK. Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell. 2009 Jun 12;137(6):1112-23. doi: 10.1016/j.cell.2009.05.037. PMID:19524513 doi:10.1016/j.cell.2009.05.037

[3] He S, Wang L, Miao L, Wang T, Du F, Zhao L, Wang X. Receptor interacting protein kinase-3 determines cellular necrotic response to TNF-alpha. Cell. 2009 Jun 12;137(6):1100-11. doi: 10.1016/j.cell.2009.05.021. PMID:19524512 doi:10.1016/j.cell.2009.05.021

[1]

[2]

[3]

6nw2

Structure of human RIPK1 kinase domain in complex with compound 11

Structural highlights

Function

See Also

References

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