Complement component 5a

3D structure of Complement Component 5a

Complement Component 5a (C5a) is a potent anaphylatoxin and a key player in the complement system, which is part of the innate immune system. C5a is a small protein fragment released from the cleavage of complement component 5 (C5) by the enzyme C5 convertase.

Structure

C5a is a 74-amino acid glycoprotein with a molecular weight of approximately 11 kDa. It is characterized by a core structure stabilized by three disulfide bonds. The 3D structure of C5a reveals a compact, globular shape that is crucial for its interaction with its receptor, C5a receptor (C5aR), on target cells.

Function

C5a plays a critical role in the immune response by acting as a powerful chemoattractant for neutrophils, eosinophils, basophils, and monocytes. It promotes the migration of these cells to sites of infection or injury. Additionally, C5a induces the degranulation of mast cells and basophils, leading to the release of histamine and other inflammatory mediators.

Receptors

C5a exerts its effects primarily through binding to the C5a receptor (C5aR), also known as CD88, which is a G protein-coupled receptor expressed on the surface of various immune cells. Another receptor, C5L2, also binds C5a but its role is less well understood and is thought to act as a decoy receptor.

Role in Disease

C5a is implicated in various inflammatory and autoimmune diseases due to its potent pro-inflammatory effects. Elevated levels of C5a are associated with conditions such as sepsis, rheumatoid arthritis, and systemic lupus erythematosus. Therapeutic strategies targeting C5a or its receptor are being explored to mitigate excessive inflammation in these diseases.

Regulation

The activity of C5a is tightly regulated in the body. It is rapidly inactivated by the enzyme carboxypeptidase N, which removes the C-terminal arginine residue, converting C5a into C5a des-Arg, a less active form.

Related Pages

• Complement system
• Anaphylatoxin
• C5a receptor
• Innate immune system