The content of complement component C2 in human plasma is generally small, and it is mainly involved in the innate immune response to infection or injury through activation of the classical complement pathway. The activation of C2 involves the binding of C1 to the Fc portion of the antibody in the antigen-antibody complex. This binding forms C1 esterase, which cleaves complement components C2 and C4. C2 is cut into two fragments, C2b and C2a. C2a can form a Mg2+ dependent complex with C4b as a C3 converting enzyme of the classical complement pathway, which causes the activation of C3 by generating fragments C3a and C3b. C3b binds to C4b2a to form the classic C5 convertase C4b2a3b. The proteolytic sites of both convertases are located on C2a. It can be seen that complement protein C2 plays an important role in the activation of the classical antibody-dependent complement pathway.
Molecular Structure of C2
C2 is a β globulin with a sugar content of 15.9%, a precipitation coefficient of 4.5S, and a molecular weight of 102kD. As a single-chain glycoprotein, the primary structure of C2 has been fully explored. C1s cleaves C2 between R223 and K224 of the C2 protein, forming a 509 residue C2a portion (C-terminus) and a 223 residue C2b portion (N-terminus). Among them, C2a is a major part of the complement pathway with transferase activity, provides a catalytic center for invertase complexes of the classical and lectin-binding pathways of complement activation.
By combining the two crystal structures of full-length C2a with or without a pseudoligand, scientists revealed the nearly active conformation of the catalytic center of the serine protease domain, while the von Willebrand factor A domain showed an open, activated metal ion Intermediate activation state of helix α7 dependent on adhesion site. Open adhesion sites may play a role in enhancing affinity for ligand C4b, similar to "inside-out" signaling in integrins. Surprisingly, the N-terminal residue of C2a was buried in the gap near the helix α7, indicating a structural transition between C2 and C2a. The extension loop on the protease domain may envelop the substrate C3 protruding anaphylatoxin domain. Together with the completion of the putative substrate-induced oxygen anion pores, it may contribute to the high substrate specificity of the invertase.
Fig. 1 Molecular structure of C2.1
C2-Related Diseases
Complement C2 deficiency is the most commonly identified complete complement deficiency. The estimated prevalence in individuals of Caucasian descent is approximately 1: 20,000, making it one of the most clinically important immunodeficiency disorders. In most cases, the deficiency is due to the homozygosity of the C2 gene deleted in exon 6, leading to incomplete deletion of C2, or in some cases to mutations in other C2 genes. For different situations, Creative Biolabs offer medical research services targeting C2 protein.
Of all C2-related diseases, the most prominent are recurrent severe infections in young children and adult systemic lupus erythematosus (SLE). Links to these diseases reflect the important role of complement C2 in innate immunity and immune tolerance. Treatment of related diseases with normal fresh frozen plasma infusions has shown therapeutic effects, but protein replacement therapies have not been evaluated to date.
Human complement C2 can be cloned and expressed in mammalian cell lines. In complement activation ELISA and hemolysis analysis, it is sensitive to C1 cleavage and restores classical complement pathway activity in C2-deficient serum. In addition, C2 can increase the deposition of C3 fragments on the human pathogen Streptococcus pneumoniae in C2-deficient serum to the same level as normal serum. Taken together, these data indicate that recombinant human C2 can restore classical complement pathway activity and can be a potential therapeutic agent for recurrent bacterial infections or SLE in patients with C2 deficiency.
Creative Biolabs offers high-quality complement component C2 related services and products, including:
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C2 Antibodies
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C2 Related Proteins
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C2 Related Array Kits
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C2 Related Peptides
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C2 Related Lysates
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Reference
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From Wikipedia: By Emw - Own work, CC BY-SA 3.0 https://commons.wikimedia.org/wiki/File:Protein_C2_PDB_2i6q.png
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