Sandbox GGC12

References: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

Function

Cytokines are protein growth factors that play a role in numerous cellular activities, primarily white blood cell response. IL-6 is a cytokine known to have many functions which include stimulating cells that give rise to blood cells and cells that function in the immune system. IL-6 aids in the antibody-mediated immunity component of the adaptive immune system by targeting cells that secrete antibodies such as B lymphocytes. It also plays in cell-mediated immunity by targeting cells such as T lymphocytes. It turns and enhances the colony of cells producing blood cells. It also aids in the production of the proteins that flux in plasma concentration in response to inflammation, which are known as acute phase response proteins.^[3]

Disease

IL-6 has been found to be involved with the maintenance of bone homeostasis, as an increase in IL-6 levels has strongly reported in illnesses such as Paget’s disease and myeloma, where significant bone loss occurs.^[4] IL-6 has also been implicated in Castleman Disease.^[5]

Relevance

IL-6 is produced is produced by wide range of cells that include not just cells of the immune system. Its production is induced by immune response, but can be affected by various antigenic factors. IL-6 binds to the IL-6 receptor of cells, which is then binded to the stignal-transducing receptor glycoprotein, known as gp130. This allows for the many functions of IL-6 in cells. Facilitating the roles that IL-6 plays in inducing cell growth and differentiation, other cytokines, immunoglobins, and acute phase proteins. IL-6-mediated signal transduction is made possible by clustering of two gp130 receptors by IL-6. IL-6 binds to binds to a single molecule of IL-6r and forms a heterodimer. The heterodimer then binds to gp130 to form a heterotrimer. An additional binding step is then needed to achieve signal transduction through clustering.^[6]

In the case of Castleman Disease, researchers have been working IL-6 with the goal that blocking the functions of IL-6 will alleviate the symptoms of afflicted patients. IL-6 blocking can be achieved through a variety of methods such as: inhibiting IL-6 production, IL-6 binding on IL-6 receptor, and interrupting intracellular signaling.^[7]

Structural highlights

This is a sample scene created with SAT to by Group, and another to make of the protein.

IL-6 is a 185 amino acid polypeptide. The structure of IL-6 is composed of four helices: A, B, C, and D. Helices A and B run in opposite direction to helices C and D. Helix A is connected to B which is connected to C; then C is connected to D. There is also an additional mini-helix. The four main helices are maintained and stabilized by a hydrophobic core.^[8]

There are water molecules throughout the IL-6 structure that form a network of hydrogen bonds that stabilize the molecule's structure.^[9]

The water molecules are shown as red spheres. The A-B loop is shown in brown with a yellow disulfide linkage near F74 which is displayed in pink. The D helix is shown in black. Q175 is shown in green. R179 is shown in blue.^[10]