The RHIM of the Immune Adaptor Protein TRIF Forms Hybrid Amyloids with Other Necroptosis-Associated Proteins

Baker, Max O. D. G.; Shanmugam, Nirukshan; Pham, Chi L.L.; Ball, Sarah R.; Sierecki, Emma; Gambin, Yann; Steain, Megan; Sunde, Margaret

doi:10.3390/molecules27113382

Cited by 3 publications

(2 citation statements)

References 58 publications

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“…Upon homo-oligomerization, this structure assembled into fibrils with the S-shaped core region rotating in each layer, which might be necessary to sterically enable RIPK3 kinase domain positioning and activity [ 65 ]. All four human RHIM-expressing proteins have the capacity to self-assemble into such homotypic oligomers with distinct structural characteristics [ 66 , 67 ].…”

Section: The Rhim Domain Assembly — An Exceptional Structurementioning

confidence: 99%

The role of RHIM in necroptosis

Riebeling

Kunzendorf

Krautwald

2022

Biochemical Society Transactions

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The RIP homotypic interaction motif (RHIM) is a conserved protein domain that is approximately 18–22 amino acids in length. In humans, four proteins carrying RHIM domains have been identified: receptor-interacting serine/threonine protein kinase (RIPK) 1, RIPK3, Z-DNA-binding protein 1 (ZBP1), and TIR domain-containing adapter-inducing IFN-β (TRIF), which are all major players in necroptosis, a distinct form of regulated cell death. Necroptosis is mostly presumed to be a fail-safe form of cell death, occurring in cells in which apoptosis is compromised. Upon activation, RIPK1, ZBP1, and TRIF each hetero-oligomerize with RIPK3 and induce the assembly of an amyloid-like structure of RIPK3 homo-oligomers. These act as docking stations for the recruitment of the pseudokinase mixed-lineage kinase domain like (MLKL), the pore-forming executioner of necroptosis. As RHIM domain interactions are a vital component of the signaling cascade and can also be involved in apoptosis and pyroptosis activation, it is unsurprising that viral and bacterial pathogens have developed means of disrupting RHIM-mediated signaling to ensure survival. Moreover, as these mechanisms play an essential part of regulated cell death signaling, they have received much attention in recent years. Herein, we present the latest insights into the supramolecular structure of interacting RHIM proteins and their distinct signaling cascades in inflammation and infection. Their uncovering will ultimately contribute to the development of new therapeutic strategies in the regulation of lytic cell death.

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Section: The Rhim Domain Assembly — An Exceptional Structurementioning

confidence: 99%

The role of RHIM in necroptosis

Riebeling

Kunzendorf

Krautwald

2022

Biochemical Society Transactions

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“…During TRIF-dependent signal pathway transduction, TRIF connects with TLR4 through TRAM as a bridge after TLR4 activation [ 118 , 119 ]. In addition to the TIR domain, TBMs also include two domains that can bind to TRAF and RIP, respectively, thereby activating downstream signal pathways [ 120 , 121 , 122 ].…”

Section: The Tlr4-mediated Signal Transduction Pathwaymentioning

confidence: 99%

Progress in Research on TLR4-Mediated Inflammatory Response Mechanisms in Brain Injury after Subarachnoid Hemorrhage

Wang

Geng²,

Zhu³

et al. 2022

Cells

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Subarachnoid hemorrhage (SAH) is one of the common clinical neurological emergencies. Its incidence accounts for about 5–9% of cerebral stroke patients. Even surviving patients often suffer from severe adverse prognoses such as hemiplegia, aphasia, cognitive dysfunction and even death. Inflammatory response plays an important role during early nerve injury in SAH. Toll-like receptors (TLRs), pattern recognition receptors, are important components of the body’s innate immune system, and they are usually activated by damage-associated molecular pattern molecules. Studies have shown that with TLR 4 as an essential member of the TLRs family, the inflammatory transduction pathway mediated by it plays a vital role in brain injury after SAH. After SAH occurrence, large amounts of blood enter the subarachnoid space. This can produce massive damage-associated molecular pattern molecules that bind to TLR4, which activates inflammatory response and causes early brain injury, thus resulting in serious adverse prognoses. In this paper, the process in research on TLR4-mediated inflammatory response mechanism in brain injury after SAH was reviewed to provide a new thought for clinical treatment.

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Roles of RIPK1 as a stress sentinel coordinating cell survival and immunogenic cell death

Clucas

Meier

2023

Nat Rev Mol Cell Biol

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The RHIM of the Immune Adaptor Protein TRIF Forms Hybrid Amyloids with Other Necroptosis-Associated Proteins

Cited by 3 publications

References 58 publications

The role of RHIM in necroptosis

The role of RHIM in necroptosis

Progress in Research on TLR4-Mediated Inflammatory Response Mechanisms in Brain Injury after Subarachnoid Hemorrhage

Roles of RIPK1 as a stress sentinel coordinating cell survival and immunogenic cell death

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