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Article on prediction of binding sites of interleukin receptor type1 using bioinformatics …


Biology Articles » Bioinformatics » Prediction of binding sites of interleukin1 type1 receptors involved in osteoarthritis » Literature review

Literature review
- Prediction of binding sites of interleukin1 type1 receptors involved in osteoarthritis

Molecules responsible for degradation of cartilage

The primary enzymes responsible for the degradation of cartilage are the matrix metalloproteinases (MMPs). These enzymes are secreted by both synovial cells and chondrocytes and are categorized into three general categories: a) collagenases; b) stromelysins; and, c) gelatinases.

 

Factors responsible for mmps synthesis

Interleukin-1 (IL-1). IL-1 is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial cells to synthesize. IL-1 was known under several other names including endogenous pyrogen, lymphocyte activating factor, haemopoetin-1 and mononuclear cell factor, amongst others.

 

 

The Interleukin-1 super family

The original members of the IL-1 superfamily are IL-1α, IL-1β, and the IL-1 Receptor antagonist (IL-1RA).IL-1α and -β are pro-inflammatory cytokines involved in immune defense against infection. IL-1α and IL-1β are produced as precursor peptides. In other words they are made as a long protein that is then processed to release a shorter, active molecule, which is called the mature protein.

IL-1 alpha:

IL-1α is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis. This cytokine is produced by many cell types but is only secreted by monocytes and macrophages. It is produced as a proprotein, which is proteolytically processed by calpain and released in a mechanism that is still not well studied. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2.

IL-1 beta:

Interleukin 1, beta, also known as IL1B, is a human gene. Interleukin-1 beta is a cytokine. IL-1β precursor is cleaved by caspase 1 (interleukin 1 beta convertase). Cytosolic thiol protease cleaves the product to form mature IL-1β. The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is produced by activated macrophages as a proprotein, which is proteolytically processed to its active form by caspase 1 (CASP1/ICE).

IL-1 Receptor antagonist (IL-1RA):

The IL-1RA is a molecule that competes for receptor binding with IL-1α and IL-1β, blocking their role in immune activation.

IL-1 Receptors:

Interleukin-1 receptor (IL-1R) is a cytokine receptor which binds interleukin 1. Two forms of the receptor exist.

  • Interleukin 1 receptor, type I: The type I receptor is primarily responsible for transmitting the inflammatory effects of interleukin-1 (IL-1) while type II receptors may act as a suppressor of IL-1 activity by competing for IL-1 binding.
  • Interleukin 1 receptor, type II: Interleukin 1 receptor, type II (IL1R2) also known as CD121b (Cluster of Differentiation 121b) is an interleukin receptor. IL1R2 also denotes its human gene.The protein encoded by this gene is a cytokine receptor that belongs to the interleukin-1 receptor family. This protein binds interleukin alpha (IL1A), interleukin beta (IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA), and acts as a decoy receptor that inhibits the activity of its ligands.
Osteoarthritis is mainly caused due to binding of IL-1 alpha with IL-1 type1 receptors. So the structural and sequence information of them is studied in order to find the binding sites of IL-1 type 1 receptor

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