Related Experiment Video
Updated: Mar 19, 2026
11:39
Identification of Functional Protein Regions Through Chimeric Protein Construction
Published on: January 8, 2019
11.0K
Structural and Functional Attributes of the Interleukin-36 Receptor
Guanghui Yi1, Joel A Ybe2, Siddhartha S Saha1
1From the Departments of Molecular and Cellular Biochemistry and.
The Journal of Biological Chemistry
|June 17, 2016
Summary
The IL-36 receptor (IL-36R) pathway is crucial for human health. This study identifies key residues in IL-1Rrp2 essential for IL-36R signaling and reveals how a common polymorphism impacts receptor function.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Interleukin-36 receptor (IL-36R) signaling plays a role in various human diseases.
- The detailed molecular mechanisms governing IL-36R structure and function remain incompletely understood.
Purpose of the Study:
- To elucidate the molecular basis of IL-36R signal transduction.
- To identify critical residues and functional domains within the IL-1Rrp2 subunit.
- To investigate the impact of genetic variations on IL-36R pathway activity.
Main Methods:
- Generation of a molecular model for the IL-36R complex.
- Establishment of a cell-based reporter assay for signal transduction analysis.
- Utilizing mutational analyses, functional assays, and examination of protein-protein interactions.
Main Results:
- Specific residues in IL-1Rrp2 were identified as crucial for cytokine recognition, protein stability, disulfide bond formation, and glycosylation, all vital for IL-36R signaling.
- Overexpression of the ectodomain (ECD) of IL-1Rrp2 or IL-1RAcP demonstrated a dominant-negative effect on IL-36R signaling.
- IL-36 cytokine binding enhanced the interaction between IL-1Rrp2 ECD and the co-receptor IL-1RAcP.
- A single nucleotide polymorphism (SNP) A471T in the Toll-interleukin 1 receptor (TIR) domain of IL-1Rrp2, found in approximately 2% of the human population, was shown to down-regulate IL-36R signaling by reducing IL-1RAcP interaction.
Conclusions:
- Key molecular determinants for IL-36R signal transduction have been identified within the IL-1Rrp2 subunit.
- The interaction between IL-1Rrp2 and IL-1RAcP is essential for IL-36R pathway activation and is modulated by IL-36 cytokines.
- A common human genetic variant (A471T) in IL-1Rrp2 impairs IL-36R signaling, potentially contributing to disease pathogenesis.
Related Concept Videos
01:20The JAK-STAT Signaling Pathway
13.7K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
13.7K
01:15Receptor Downregulation in MVBs
3.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
3.0K
01:24T Cell Types and Functions
3.1K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.1K
01:27Transducer Mechanism: Enzyme-Linked Receptors
4.8K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
4.8K
02:26NF-κB-dependent Signaling Pathway
10.2K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
10.2K
01:25Selectins
4.7K
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain,...
4.7K