CD55 - CD55 molecule |Elisa - Clia - Antibody - Protein

Background

CD55, also known as decay-accelerating factor (DAF), is a glycoprotein that plays a critical role in regulating the complement system, a part of the innate immune response. The primary function of CD55 is to protect host cells from complement-mediated damage by inhibiting the formation of C3 and C5 convertases, key enzymes in the complement activation pathways. CD55 is widely expressed on the surface of many cell types, including erythrocytes, leukocytes, endothelial cells, and epithelial cells. Its expression is essential for preventing unintended complement activation on host tissues, which could lead to cell lysis and tissue damage.

CD55 is particularly important in safeguarding cells from the alternative pathway and classical pathway of complement activation. The complement system is a major defense mechanism that helps the body clear pathogens through opsonization, inflammation, and lysis of infected or foreign cells. By regulating this system, CD55 ensures that the complement system does not damage self-cells, thus maintaining tissue integrity during immune responses.

Protein Structure

CD55 is a glycosylphosphatidylinositol (GPI)-anchored protein, meaning it is attached to the cell membrane through a GPI anchor. This allows for its placement on the extracellular surface of the cell membrane, where it can interact with complement proteins. CD55 has several key structural features:

1. Short Cytoplasmic Tail:

• CD55 has a short cytoplasmic domain, which is involved in anchoring the protein to the inner leaflet of the cell membrane. However, because it is GPI-anchored, CD55 does not have a transmembrane domain.

1. Extracellular Domains:

• CD55 consists of four complement control protein (CCP) domains, also known as short consensus repeats (SCRs). Each of these domains is roughly 60 amino acids long and contains conserved cysteine residues that form disulfide bonds, giving the protein a highly stable, globular structure.
• These CCP domains are responsible for the functional interactions with components of the complement system, particularly C3b and C4b. The binding of CD55 to these complement components inhibits the assembly of the C3 and C5 convertases, thus accelerating the decay of these complexes and preventing further complement activation.

1. Glycosylation:

• CD55 is heavily glycosylated, with several N-linked glycosylation sites located on its extracellular domains. This glycosylation contributes to the protein's stability and helps protect it from proteolytic degradation. Additionally, the glycosylation sites may play a role in modulating CD55's interactions with complement proteins and other cell surface molecules.

1. GPI Anchor:

• The GPI anchor attaches CD55 to the outer membrane of the cell. This lipid anchor allows CD55 to be part of specialized membrane microdomains, such as lipid rafts, which are important for organizing signaling complexes and for facilitating efficient interactions with other membrane proteins.

Classification and Subtypes

CD55 is classified as a complement regulatory protein, with a specific role in inhibiting the complement system. While CD55 does not have any subtypes, it belongs to a broader family of complement control proteins (CCPs) that include other regulators like CD46 (membrane cofactor protein) and CD59. These molecules all serve to protect host cells from complement attack, but each has a distinct mechanism of action. CD55, specifically, accelerates the decay of complement convertases, while other complement regulators like CD59 block the formation of the membrane attack complex (MAC).

Function and Biological Significance

CD55’s primary function is to inhibit the complement cascade by preventing the formation and stabilization of C3 and C5 convertases in both the classical and alternative complement pathways. These convertases are essential for cleaving C3 and C5 into their active forms, which then promote the downstream processes of opsonization, inflammation, and cell lysis. By disrupting the formation of these convertases, CD55 effectively inhibits complement activation and protects host cells from immune-mediated damage.

Key functions of CD55 include:

Regulation of Complement Activation:

• CD55 binds to the complement proteins C3b and C4b, which are essential components of the convertases in both the classical and alternative complement pathways. By binding to these proteins, CD55 accelerates the dissociation (decay) of C3/C5 convertases, preventing the downstream cleavage of complement components that would otherwise lead to cell lysis or inflammation.

Protection of Host Cells:

• CD55 is essential for protecting host cells from complement-mediated lysis. It ensures that complement activation is limited to foreign or pathogen-infected cells, preventing the inappropriate destruction of healthy host tissues. Cells without functional CD55 are more susceptible to complement attack, which can lead to disorders such as paroxysmal nocturnal hemoglobinuria (PNH), where red blood cells are destroyed by complement activation due to defective GPI anchors.

Role in Inflammation:

• CD55 also plays a role in modulating inflammatory responses. By controlling complement activation, CD55 prevents excessive production of pro-inflammatory mediators such as anaphylatoxins (C3a, C5a), which are potent triggers of inflammation. This regulatory function helps to maintain balance in the immune system and prevents unnecessary tissue damage during immune responses.

Interaction with Pathogens:

• Some pathogens have evolved mechanisms to hijack CD55 to avoid complement-mediated destruction. For example, certain viruses and bacteria bind to CD55 to protect themselves from the host’s immune system. This interaction allows pathogens to persist in the host and evade immune clearance.

Adhesion Molecule:

• Beyond its role in complement regulation, CD55 has been implicated in cellular adhesion processes. It interacts with other cell surface molecules, such as CD97, a member of the EGF-TM7 family of proteins. This interaction is thought to play a role in immune cell trafficking and may contribute to processes such as leukocyte extravasation during inflammation.

Clinical Issues

Paroxysmal Nocturnal Hemoglobinuria (PNH):

• A key clinical condition associated with CD55 dysfunction is paroxysmal nocturnal hemoglobinuria (PNH), a rare acquired disorder in which red blood cells are prone to complement-mediated lysis. PNH arises due to mutations in the PIGA gene, which is involved in the biosynthesis of GPI anchors. Without a functional GPI anchor, CD55 (and other GPI-anchored proteins such as CD59) cannot attach to the cell membrane, leaving red blood cells vulnerable to complement attack. This results in episodes of hemolysis, leading to symptoms such as fatigue, jaundice, and an increased risk of thrombosis.

Autoimmune Diseases:

• Abnormal CD55 function or expression may be implicated in autoimmune diseases such as systemic lupus erythematosus (SLE), where complement dysregulation plays a role in tissue damage. In such conditions, inadequate expression of CD55 on host tissues could contribute to excessive complement activation and inflammation, exacerbating autoimmune responses.

Cancer:

• Altered expression of CD55 has been observed in various cancers, including colorectal cancer and breast cancer. Tumors may upregulate CD55 expression as a mechanism to evade complement-mediated destruction, allowing cancer cells to survive and proliferate. CD55 overexpression in tumors could be a mechanism of immune evasion, contributing to the tumor's resistance to immune surveillance.

Therapeutic Targeting:

• Targeting CD55 has potential therapeutic applications, particularly in conditions where complement regulation is defective, such as PNH, or in cancers where CD55 is overexpressed. Inhibitors that block the interaction of CD55 with complement components could be used to enhance the immune system's ability to target cancer cells. Alternatively, increasing CD55 expression in autoimmune diseases might help to mitigate excessive complement activation and inflammation.

Summary

CD55, or decay-accelerating factor (DAF), is a GPI-anchored protein that plays a vital role in protecting host cells from complement-mediated damage. It achieves this by inhibiting the formation of C3 and C5 convertases, key enzymes in the complement system, thereby preventing inappropriate complement activation on healthy cells. CD55 consists of four complement control protein (CCP) domains that interact with C3b and C4b, accelerating the decay of convertase complexes. Clinically, CD55 dysfunction is associated with conditions such as paroxysmal nocturnal hemoglobinuria (PNH), autoimmune diseases, and cancer. In addition to its role in complement regulation, CD55 may also be involved in immune cell adhesion and pathogen interactions. Targeting CD55 holds therapeutic potential in diseases where complement dysregulation plays a central role. Understanding the molecular function of CD55 is essential for developing treatments for these complement-related disorders.