AICDA - Activation Induced Cytidine Deaminase | Elisa - Clia - Antibody - Protein

Background:

Activation-Induced Cytidine Deaminase (AID) is a crucial enzyme involved in the processes of somatic hypermutation (SHM) and class switch recombination (CSR) in B cells, which are fundamental mechanisms for generating antibody diversity in the immune system. Somatic Hypermutation (SHM): AID introduces point mutations in the variable regions of immunoglobulin genes during B cell activation. This process enhances the diversity of antibodies, allowing for the generation of high-affinity antibodies against specific antigens. Class Switch Recombination (CSR): AID mediates the exchange of constant regions (C regions) of immunoglobulin heavy chain genes, resulting in the production of antibodies with different effector functions (e.g., IgM to IgG, IgA, or IgE). This process is essential for optimizing the immune response to different types of pathogens. Despite its critical role in antibody diversification, AID activity can also lead to genomic instability and the development of B cell lymphomas if not tightly regulated. Thus, AID regulation is an area of active research in immunology and cancer biology.

Protein Structure:

• Molecular Weight: Approximately 24 kDa.
• Primary Structure: Composed of 198 amino acids.
• Secondary and Tertiary Structure: AID has a deaminase domain that is responsible for its catalytic activity, with structural motifs essential for binding DNA and catalyzing deamination.
• Post-translational Modifications: AID activity is regulated by phosphorylation, ubiquitination, and potentially other modifications, which affect its localization and function.

Classification and Subtypes:

• Protein Family: AID belongs to the APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) family of cytidine deaminases.
• Subtypes: While AID itself does not have subtypes, it is part of a broader family that includes other APOBEC enzymes involved in various RNA and DNA editing processes.

Function and Biological Significance:

• Somatic Hypermutation (SHM): AID introduces point mutations in the variable regions of immunoglobulin genes, increasing the diversity of antibodies and enabling the immune system to adapt to new antigens.
• Class Switch Recombination (CSR): AID facilitates the recombination of immunoglobulin heavy chain constant regions, allowing B cells to produce different classes of antibodies (e.g., IgG, IgA, IgE) without altering antigen specificity.
• Gene Conversion: In some species, AID is involved in gene conversion, another mechanism of diversifying the antibody repertoire.

Interactions:

• DNA: AID binds to single-stranded DNA regions during transcription to deaminate cytosine bases to uracil.
• UNG (Uracil-DNA Glycosylase): This enzyme recognizes and removes uracil residues introduced by AID, initiating the base excision repair pathway.
• MSH2/MSH6 (MutS Homologs): These mismatch repair proteins help process AID-induced mutations and contribute to SHM and CSR.

Clinical Issues:

• Immunodeficiencies: Mutations or deficiencies in AID can lead to hyper-IgM syndrome type 2, characterized by elevated levels of IgM and reduced levels of other antibody classes, resulting in immunodeficiency.
• Autoimmunity: Dysregulated AID activity can lead to inappropriate mutations and chromosomal translocations, contributing to autoimmune diseases such as lupus and rheumatoid arthritis.
• Cancer: Aberrant AID expression and activity are implicated in the development of B-cell lymphomas and other cancers due to its potential to cause mutations and genomic instability.

Summary:

Activation-Induced Cytidine Deaminase (AID) is a pivotal enzyme in the adaptive immune system, essential for the diversification of antibodies through somatic hypermutation and class switch recombination. Its precise regulation and function are critical for effective immune responses, while its dysregulation can lead to immunodeficiency, autoimmunity, and cancer. Understanding AID's role and mechanisms continues to be a significant area of research in immunology and oncology.