CD40 receptor complex

Definition

Target type: cellularcomponent

A protein complex that contains at least CD40 (a cell surface receptor of the tumour necrosis factor receptor (TNFR) superfamily), and other signaling molecules. [GOC:BHF, PMID:20614026, PMID:9221764]

The CD40 receptor complex is a multi-protein assembly that plays a crucial role in immune cell signaling. It is primarily found on the surface of antigen-presenting cells (APCs), such as B cells, dendritic cells, and macrophages, and interacts with its ligand, CD40 ligand (CD40L), expressed on activated T cells. The complex consists of the CD40 receptor itself, which is a type I transmembrane protein with an extracellular domain containing four immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic domain. The cytoplasmic domain of CD40 interacts with various adaptor proteins and signaling molecules, leading to the activation of downstream pathways that regulate immune responses.

The CD40 receptor complex is thought to be organized into clusters or microdomains on the cell surface, facilitating efficient signal transduction. These microdomains are enriched with specific lipid rafts and signaling molecules that are critical for the proper function of the complex.

Upon CD40L binding, the CD40 receptor undergoes a conformational change, leading to the recruitment of various adaptor proteins and signaling molecules to the cytoplasmic domain. These include TRAF proteins (TRAF2, TRAF3, TRAF5, and TRAF6), which are key mediators of CD40 signaling. TRAF proteins interact with the CD40 cytoplasmic domain through their TRAF domains and initiate the activation of downstream signaling pathways, such as the NF-κB and MAPK pathways.

The NF-κB pathway plays a critical role in the regulation of gene expression involved in immune responses, such as the production of cytokines and chemokines. Activation of the NF-κB pathway by CD40 signaling leads to the expression of various genes, including those encoding for CD80, CD86, and MHC class II, which are essential for T cell activation and differentiation.

The MAPK pathway, on the other hand, is involved in the regulation of cell proliferation, differentiation, and survival. CD40 signaling activates the MAPK pathway, leading to the phosphorylation of various MAPK proteins, including ERK, JNK, and p38. These phosphorylated MAPKs then translocate to the nucleus and regulate the expression of target genes.

In addition to TRAF proteins, other signaling molecules that interact with the CD40 cytoplasmic domain include the protein kinase C (PKC) family, the phosphatidylinositol 3-kinase (PI3K) family, and the Src family kinases. These molecules contribute to the activation of downstream signaling pathways, further enhancing the complexity and diversity of CD40 signaling.

The cellular component of the CD40 receptor complex is therefore a dynamic and complex structure that plays a pivotal role in immune cell activation and regulation. The interactions between the CD40 receptor, its ligand, and various adaptor proteins and signaling molecules allow for precise and efficient signal transduction, leading to the induction of diverse immune responses. Understanding the intricate details of the CD40 receptor complex is crucial for developing novel therapeutic strategies targeting immune system dysregulation.'
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Proteins (4)

Compounds (120)