Structural basis for amyloid fibril assembly by the master cell-signaling regulator receptor-interacting protein kinase 1
From Proteopedia
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| - | ==Structural basis for amyloid fibril assembly by the master cell-signaling regulator receptor-interacting protein kinase 1== | + | =='''Structural basis for amyloid fibril assembly by the master cell-signaling regulator receptor-interacting protein kinase 1'''<ref>PMID: 41168207<ref/>== |
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | <StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''> | ||
This is a default text for your page '''Rida Shahnawaz Khan/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs. | This is a default text for your page '''Rida Shahnawaz Khan/Sandbox 1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs. | ||
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== Disease == | == Disease == | ||
| - | RIPK1 has been reported to be involved in many neurodegenerative diseases such as AD, ALS and MS. In Alzheimer's disease, it has been shown to regulate microglial function by modulating cell inflammation. In Amyotrophic Lateral Sclerosis, RIPK1, along with RIPK3 and MLKL, has been shown to contribute to the demyelination and degeneration of neurons. | + | RIPK1 has been reported to be involved in many neurodegenerative diseases such as AD, ALS and MS. In Alzheimer's disease, it has been shown to regulate microglial function by modulating cell inflammation.<ref>PMID:28904096<ref/> In Amyotrophic Lateral Sclerosis, RIPK1, along with RIPK3 and MLKL, has been shown to contribute to the demyelination and degeneration of neurons.<ref>PMID:27493188<ref/> |
| - | RIPK1 was also linked to an auto-inflammatory syndrome, CRIA syndrome. It is caused by a mutation in RIPK1, which prevents it from being cleaved, leading to uncontrolled cell death and chronic inflammation. | + | RIPK1 was also linked to an auto-inflammatory syndrome, CRIA syndrome. It is caused by a mutation in RIPK1, which prevents it from being cleaved, leading to uncontrolled cell death and chronic inflammation.<ref>PMID:31827281<ref/> |
== Structural Determination == | == Structural Determination == | ||
The primary methods employed to determine the structure of homomeric RIPK1 fibrils were solid-state NMR and electron microscopy. Cryo-probe detection was used in NMR to increases sensitivity by reducing electronic noise. Negative staining electron microscopy was used to capture initial images, while cryo EM was used for further structural determination. | The primary methods employed to determine the structure of homomeric RIPK1 fibrils were solid-state NMR and electron microscopy. Cryo-probe detection was used in NMR to increases sensitivity by reducing electronic noise. Negative staining electron microscopy was used to capture initial images, while cryo EM was used for further structural determination. | ||
| - | == Structural | + | == Structural Highlights == |
RIPK1 has an N-terminal kinase domain, an intervening disordered region and a C-terminal death domain. The disordered region consists of the RHIM (RIP homotypic interaction motif), which is represented by a tetrapeptide with a consensus sequence of (V/I)-Q-(V/I/L/C)-G. | RIPK1 has an N-terminal kinase domain, an intervening disordered region and a C-terminal death domain. The disordered region consists of the RHIM (RIP homotypic interaction motif), which is represented by a tetrapeptide with a consensus sequence of (V/I)-Q-(V/I/L/C)-G. | ||
Revision as of 10:04, 29 November 2025
==Structural basis for amyloid fibril assembly by the master cell-signaling regulator receptor-interacting protein kinase 1[1] or to the article describing Jmol [2] to the rescue.
Function
RIPK1 (Receptor-Interacting Protein Kinase 1) is a protein that plays a central role in cell death and survival pathways, regulating inflammation and maintaining homeostasis. When polyubiquitinated, RIPK1 promotes cell proliferation and differentiation. Here, it acts as part of the TNFR signalling pathway to activate the NF-κB transcription factors. Conversely, in the absence of polyubiquitination, it can form a complex with FADD and caspase 8 to trigger apoptosis. In the case of caspase activity blockage, the assembly of RIPK1/RIPK3 fibrils can trigger necroptosis. The signalling pathway starts with the self-association of RIPK1, leading to the assembly of heteromeric RIPK1-RIPK3 fibrils (canonical necrosome), finally resulting in MLKL oligomerisation to trigger necroptosis.
Disease
RIPK1 has been reported to be involved in many neurodegenerative diseases such as AD, ALS and MS. In Alzheimer's disease, it has been shown to regulate microglial function by modulating cell inflammation.[3]
