Integrin alpha-M (CD11b) I-domain (CD11b)

Integrin alpha-M (CD11b), specifically its I-domain, is a critical component of the heterodimeric Complement Receptor 3 (CR3), also known as Mac-1 (UniProt P11215) [1]. This domain serves as the primary binding site for a diverse array of ligands, including the complement fragment iC3b, intercellular adhesion molecule-1 (ICAM-1), and fibrinogen (PubMed: 10603370) [2]. By mediating leukocyte adhesion to the endothelium and subsequent migration into tissues, the CR3 alpha-M I-domain plays a central role in the innate immune response and inflammatory processes (PubMed: 25661156) [3]. In pathological contexts, overactivation or dysregulation of this receptor is linked to autoimmune diseases like systemic lupus erythematosus and neurodegenerative conditions such as Alzheimer's disease, where it facilitates microglial-mediated synapse loss (PubMed: 18204446; PubMed: 27031984) [4, 5]. Therapeutic strategies targeting the I-domain include small-molecule agonists like Leukadherin-1, which aim to stabilize the receptor in a specific conformation to modulate leukocyte recruitment and promote immune tolerance (PubMed: 21248295) [6]. However, pharmacological intervention must be carefully balanced to avoid compromising essential host defense mechanisms and increasing infection risk (PubMed: 25661156) [3].

Other names

CD11bITGAMMac-1 alpha subunitCR3 alpha chainMO1SLEB6

Allosteric modulation of the I-domain to regulate ligand binding affinity and leukocyte recruitment.