Anaphylatoxin Family Related Drug Discovery Products
Membrane protein stable cell lines are widely used in many areas of biomedical research. Creative Biolabs can offer membrane protein stable cell lines to stablish in vitro models for High Throughput Screening.
Creative Biolabs offers high-quality, innovative tools to help research groups accelerate membrane protein drug discovery. They can be found by targets. If there is no product that meets your needs, please contact us.
The anaphylatoxins (AT) C3a, C5a, and C5a-desArg were cleaved by proteases in response to complement activation, and are widely regarded as pro-inflammatory polypeptides. Chemotaxis, mast cell activation, and macrophage activation are some of their well-known effector actions. Local proteases produced by pathogens, cells, or contact systems can also produce ATs within tissues. The pleiotropic physiological implications of this local AT production, which go beyond inflammation, make them crucial.
Creative Biolabs offers a range of anaphylatoxin family drug discovery assays and products with our well-established high-efficient drug discovery strategy in a timely and cost-effective manner:
Overview of Anaphylatoxin Receptors
- C3aR
The C3aR, which has a Kd of roughly 1 nM for selectively binding C3a, does not recognize the desarginated version of C3a or C5a. With 482 amino acids and a sulfated tyrosine at position 174, it is a 54 kDa protein with two glycosylation sites at asparagines 9 and 195. The C3aR is unique among the AT receptors in that it has a remarkable sizable second extracellular loop, which makes up about a third of its size and is crucial for ligand binding. Heterotrimeric G-proteins help to increase intracellular signal transduction when C3a binds to the C3aR. The pertussis toxin receptor (C3aR) in neutrophils communicates via G-proteins (presumably Gαi) and mobilizes calcium fluxes from the extracellular medium but not from intracellular reserves. For signal transduction, C3aR may also come into contact with Gα16 that is not susceptible to pertussis toxin. C3aR may couple to Gα12 or Gα13 in endothelial cells. Activation of protein kinase C by phospholipase C and the mitogen-activated protein (MAP) kinases Erk1 and Erk2 in astrocytes are downstream signaling.
- C5aR
While C3a and C3a-desArg are not recognized, the C5aR (CD88) binds C5a and C5a-desArg with varying degrees of affinity. 350 amino acids make up the 42 kDa protein C5aR, with asparagine at position 5 being glycosylated. Heterotrimeric G-proteins are essential for the C5aR signaling process. The Gαi2 or Gα16 pertussis toxin-insensitive alpha units are primarily responsible for this. Calcium is released from both intracellular reserves and the extracellular media when C5a binds to C5aR. Following activation, β-arrestins 1 and 2 attach to C5aR, directing it to pits covered in clathrin for receptor internalization. Different cell types express C5aR. Neutrophils, eosinophils, basophils, monocytes/macrophages, mast cells, and DCs all have the highest levels of expression.
Anaphylatoxin Receptors Drug Discovery
C5a and the C5aR in particular have been viewed as desirable pharmaceutical targets because of their potent pro-inflammatory characteristics. While C5aR targeting might seem like an appealing strategy for treating acute inflammation, long-term strategies should take into account any direct or indirect effects of AT receptor signaling on adaptive immune responses, cell apoptosis, and tissue regeneration/fibrosis that may have an impact on such therapies.
