CD59 is a protein anchored to the surface of cell membranes through glycosylphosphatidylinositol (GPI), and was first identified as a regulator of the complement terminal pathway. CD59 works by binding to the C8 / C9 component of the assembly membrane attack complex (MAC), inhibits the formation of lytic pores, and thus protects the host cell. Structurally, CD59 is a small, highly glycosylated GPI connexin protein with a broad expression profile. Functionally, CD59's role in complement regulation is clearly defined, but studies have shown that changes in its anchoring mode and location can trigger a series of signal transmissions independent of the complement system, suggesting that CD59 has a role other than complement inhibitors. Correspondingly, the abnormal expression of CD59 not only causes a variety of autoimmune diseases, but its high expression on the surface of tumor cells is also closely related to tumor resistance when treated with monoclonal antibody drugs. Creative Biolabs offers a variety of component-related services and complement system-realted products for CD59, which can help you further reveal its mechanism of action in different physiological processes.
Fig. 1 Protein structure of CD59.1
CD59 Distribution, Structure and Function
The human CD59 gene is located on the broken arm of chromosome 11 and is about 27kb long. Its protein consists of 128 amino acids, and the 25 amino acid residues at the N-terminus are signal peptides. The C-terminus is anchored to the cell membrane surface by GPI, and participates in signal transduction through GPI and lipid raft. CD59 protein contains 5 disulfide bonds, which not only maintains its spatial structure, but also maintains its molecular properties stable.
The tissue expression of CD59 is very extensive, and it is expressed in lung, liver, kidney, heart, skin, nervous system and various blood cells. Its main function is to bind to C8α and C9 in the end stage after activation of the complement system, and inhibit MAC formation, which in turn protects cells from MAC-mediated cell lysis effects. In addition, CD59 also performs a number of functions that are not related to the complement system. It can be used as a natural ligand of CD2 to participate in T cell adhesion and transduction of cell activation signals, to participate in the proliferation and differentiation of B cells and natural killer cells, and to participate in apoptosis signals.
C1-INH Related Diseases
Low expression of CD59 due to gene defects can lead to many diseases. The mutations in PIG-A gene in patients with paroxysmal sleep hemoglobinuria (PNH) result in impaired GPI of CD59 protein that cannot function normally on erythrocyte and platelet membranes, leaving erythrocytes and platelets vulnerable to complement attack and lysis under pathological conditions. This loss of CD59 function on the surface of red blood cells can also occur in immune diseases including autoimmune hemolytic anemia (AIHA) and aplastic anemia (AA), leading to various corresponding clinical responses. In addition, the abnormal physiological environment caused by some other diseases will also affect the function of CD59. Lys41 of CD59 is a potential glycosylation site. Because it is very close to the key action site of CD59 protein, glycosylation of Lys41 will cause the structural change of CD59 and lose most of its functions. This abnormally glycosylated CD59 protein has been detected in diabetic patients, a phenomenon that causes normal cells to be attacked by complement, causing various vascular-related complications.
The abnormally high expression of CD59 also affects human health. Antibody-dependent cell-mediated toxic effects (CDC) are considered to be the main mechanism of action of antibodies in the treatment of tumors. However, the expression of CD59 in almost all tumor tissues is significantly higher than that in homologous normal tissues. These CD59, which are highly expressed on the surface of cancer cells, reduce the killing effect of complement and cause tumor cells to become resistant or non-responsive to antibody treatment. In terms of application, CD59 can be used as a biomarker to predict the occurrence of tumors and the efficacy of antibody drugs. It can also reduce the expression level of CD59 by gene therapy or inhibitors to improve the tumor treatment effect of antibodies.
Creative Biolabs offers a full range of complement component-related services and products, please do not hesitate to contact us for more details.
Reference
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From Wikipedia: By Emw - Own work, CC BY-SA 3.0 https://commons.wikimedia.org/wiki/File:Protein_CD59_PDB_1cdq.png
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