CD59

Background

MAC-IP (MAC-inhibitory protein), also known as CD59 or membrane inhibitor of reactive lysis (MIRL), is a cell surface glycoprotein that in humans encoded by the CD59 gene. This gene spans over 20 kb of DNA and contains four exons. The precursor protein encoded by the CD59 gene has 128 amino acids, 25 of which are amino-terminal signal peptides, and 26 amino acid hydrophobic sequences at the carboxyl-terminal, which provide signals for GPI anchoring. The mature protein contains a backbone of 77 amino acids with the GPI anchor attached to Asn77. The structure of CD59 in solution was recently determined by NMR spectroscopy. The protein is folded into a disk-like domain with clustered desulfur bonds at the hydrophobic center and four ring-like extensions protruding from the disk.

Fig.1 The structure of human CD59. Distributed under CC BY-SA 3.0, from Wiki, without modification.

MAC-IP is a crucial regulator that protects autologous cells from the terminal effector mechanism of the complement cascade. MAC-IP can bind to C8 in the C5b-8 complex and block the uptake and polymerization of C9, interfering with the assembly of a fully functional MAC, thereby inhibiting the formation of cytolytic pore on host cell surfaces. Sometimes, MAC-IP may also bind to C9 in partially assembled MAC complexes. Besides, MAC-IP has been revealed to be involved in lymphocyte signal transduction. MAC-IP can bind to human CD2, leading to T cell costimulation. Mutations with loss of function in the CD59 gene are associated with several diseases such as hemolytic anemia, thrombosis, and cerebral infarction.

CD59 Functional Service

Creative Biolabs provides a comprehensive range of CD59-related products, encompassing anti-CD59 Antibodies, CD59 ELISA Assay kits, CD59 Proteins, CD59 Blocking Peptides, CD59 Lysates, and anti-CD59 Aptamer, which are designed for research on immune regulation, complement activation, and cell survival, serving a wide array of applications in autoimmune diseases, cancer immunology, and transplantation.

CD59 functional testing is essential for understanding its role in complement inhibition and cellular protection. Functional assays like ELISA, flow cytometry, and complement-mediated hemolysis assays can measure CD59 activity in preventing complement-induced cell damage. For instance, ELISA can be used to quantify soluble CD59 levels in serum or other biological fluids, providing valuable information about complement regulation. Using anti-CD59 antibodies in ELISA assays has demonstrated how CD59 can protect tumor cells from immune destruction, thereby promoting cancer cell survival.

Fig.2 Measurement of soluble CD59 in peritoneal dialysis patients using ELISA.¹

Another key application has been in autoimmune disease models, where CD59 activity correlates with tissue damage and inflammation. CD59 inhibition using blocking peptides demonstrates increased complement activity and cell lysis, confirming CD59’s crucial role in complement inhibition. Functional testing of CD59 also helps in evaluating therapeutic agents targeting complement pathways in diseases such as paroxysmal nocturnal hemoglobinuria (PNH).

Creative Biolabs provides CD59-functional services, including custom assays, complement inhibition studies, and immune modulation testing, ensuring high-quality data and personalized service to accelerate your research development.

Reference

1. Faria, Bernardo, et al. "Soluble CD59 in peritoneal dialysis: a potential biomarker for peritoneal membrane function." Journal of Nephrology 34 (2021): 801-810. Distributed under Open Access license CC BY 4.0, without modification.