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Front Immunol. 2018 Nov 26;9:2716. doi: 10.3389/fimmu.2018.02716. eCollection 2018.

Structural Immunology of Complement Receptors 3 and 4.

Frontiers in immunology

Thomas Vorup-Jensen, Rasmus Kjeldsen Jensen

Affiliations

  1. Biophysical Immunology Laboratory, Department of Biomedicine, Aarhus University, Aarhus, Denmark.
  2. Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, Denmark.
  3. Department of Molecular Biology and Genetics-Structural Biology, Aarhus University, Aarhus, Denmark.

PMID: 30534123 PMCID: PMC6275225 DOI: 10.3389/fimmu.2018.02716

Abstract

Complement receptors (CR) 3 and 4 belong to the family of beta-2 (CD18) integrins. CR3 and CR4 are often co-expressed in the myeloid subsets of leukocytes, but they are also found in NK cells and activated T and B lymphocytes. The heterodimeric ectodomain undergoes considerable conformational change in order to switch the receptor from a structurally bent, ligand-binding in-active state into an extended, ligand-binding active state. CR3 binds the C3d fragment of C3 in a way permitting CR2 also to bind concomitantly. This enables a hand-over of complement-opsonized antigens from the cell surface of CR3-expressing macrophages to the CR2-expressing B lymphocytes, in consequence acting as an antigen presentation mechanism. As a more enigmatic part of their functions, both CR3 and CR4 bind several structurally unrelated proteins, engineered peptides, and glycosaminoglycans. No consensus motif in the proteinaceous ligands has been established. Yet, the experimental evidence clearly suggest that the ligands are primarily, if not entirely, recognized by a single site within the receptors, namely the metal-ion dependent adhesion site (MIDAS). Comparison of some recent identified ligands points to CR3 as inclined to bind positively charged species, while CR4, by contrast, binds strongly negative-charged species, in both cases with the critical involvement of deprotonated, acidic groups as ligands for the Mg

Keywords: cell adhesion; complement; complement receptors; divalent metal ions; drug repurposing; innate immunity; integrins; von willebrand facor A (VWA) domain

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