Tumor necrosis factors
The TNF / TNFR superfamily (full tumor necrosis factor / tumor necrosis factor receptor superfamily ) is a system of currently more than 40 identified ligand and receptor proteins, which are usually produced by cells of the immune system and cell proliferation, cell survival, cell differentiation and apoptosis of responsive cells affect: For this purpose, interact membrane-bound and / or soluble ligands of the TNF superfamily, with one or often more specific membrane-bound and / or soluble receptors, which form the corresponding TNF receptor superfamily .. the function this complex system of ligands and receptors can be seen in particular in the regulation of immunological processes.
TNF superfamily ligands
The TNF superfamily ligands arise mostly as a type 2 transmembrane proteins, ie proteins whose N -terminus is located intracellularly. Each three monomers of a corresponding ligand combine non-covalently to a biologically active trimer. The extracellularly located protein surfaces of the different ligands have little resemblance to each other, which explains its receptor specificity. From some of the membrane-bound ligand is released by proteolytic cleavage usually by metalloproteinases ( induced by various stimuli), a soluble form. Some TNF superfamily ligands are formed but also as soluble proteins and membrane-anchored form secondary heterotrimeric complexes.
TNF superfamily receptors
TNF- like receptors are transmembrane proteins of type 1, that is transmembrane protein whose C -terminus is intracellular. As a typical feature possess the receptors of the TNFR superfamily one to six extracellularly located cysteine -rich domain (s). As the ligands of the TNF / TNFR superfamily receptors also form the trimers. Some of the receptors, such as TNF receptor type 1 ( TNFR1 ), type 2 TNF receptor ( TNFR2 ), CD40, or trimerize before binding to their ligands, located on the N-terminus of the respective receptor, called preligand assembly domain ( PLAD ) is dependent. Receptor activation by different cytoplasmic adapter molecules can bind to the intracellular domain of the respective receptor. This in turn can each have different intracellular signaling cascades are set in motion at the end of an appropriate cellular response is. Depending on various Regulationsmechenismen it is also possible that a receptor ( such as TNFR1 ) trigger different signaling cascades in motion and thus different ( even opposing ) can induce cellular responses. Some of the receptors ( by various stimuli ) soluble forms can be removed, which then neutralize the accompanying ligands. According to the intracellular sequences of the receptors, the TNF receptor superfamily can be divided into three groups: