C1r Proenzyme

Background

Overview of C1r Proenzyme

C1 is the first molecule to function in the classical pathway of complement, and C1r is a crucial part of the C1 complex. C1r initially exists in the form of C1r proenzyme, which is an inactive single-chain 92 kD protein. The C1r proenzyme is widely believed to be the original form of the C1r enzyme.

Its Gene ID: 715, UniProtKB ID: P00736, and OMIM ID: 613785.

Function of C1r Proenzyme

C1 is a non-covalent complex consisting of two C1r, one C1q, and two C1s molecules. Typically, C1q binds to specific sites on IgM or IgG. The binding of C1q to immune complexes can trigger a stimulatory signal, which leads to the activation of C1r proenzymes in the complex into C1r enzymes. Next, the C1r enzymes stimulate and activate the C1s protease in the complex to produce activated C1s molecules that further initiate reactions in the classical pathway.

Fig.1 The complement cascade.^1,3

Mechanism of C1r Proenzyme

The first complex of complement, C1, is activated by signals induced by its subcomponents C1r and C1s. C1s is reported to be incapable of self-activation and its activation is dependent on the mediation of specific active sites. Notably, the origin of the protease cleavage that induces C1r activation in C1 has not been determined. Currently, the protease activity of C1q has not been characterized, and therefore, the first proteolytic event of C1 activation is attributed to C1r. Furthermore, data show that C1r is activated in C1 via an autocatalytic pathway.

C1r Proenzyme Assays

CH50 is a core indicator for characterizing the total hemolytic activity of the classical pathway. Therefore, the modified CH50 can be used to describe the activity of the C1r proenzyme.

What Can We Do for You?

As a leader in complement research, Creative Biolabs will provide a variety of products for your complement project. Our complementary products include but are not limited to the products listed below.

• Native Human Complement C1r Enzyme Protein
• Native Human Complement C1r Proenzyme Protein
• Human Anti-C Reactive Protein Autoantibody ELISA Kit

Please contact our complement team for more information on complement products.

C1r Proenzyme Functional Service

Creative Biolabs provides a comprehensive range of C1r proenzyme related products, including native human complement C1r proenzyme protein. These products can effectively carry out C1r proenzyme related experiments and thus play an important role in your research.

Fig.2 C1r domain structure and secretion pattern.^2,3

Heterozygous missense mutations or in-frame insertion/deletion mutations in the complement 1 subunits C1r and C1s are associated with periodontal Ehlers-Danlos syndrome (pEDS). pEDS is a specific subtype of Ehlers-Danlos syndrome characterized by early and severe periodontal destruction, as well as connective tissue abnormalities. Extensive functional studies have been conducted on 16 C1R variants linked to pEDS. These variants were analyzed through in vitro overexpression in specific cells, followed by techniques such as western blotting, size exclusion chromatography, and surface plasmon resonance analysis. The results showed that overexpression of C1R variants in these cells did not allow for their integration into the C1 complex; instead, it resulted in catalytic activity of C1r and C1s being present outside the cell. In addition to the C1R missense variants that disrupt the C1q binding site, the pEDS variants exhibited different cellular effects compared to the wild-type C1r. These included intracellular retention of C1r fragments, secretion of aggregates, and the creation of new cleavage sites for C1r.2,3

Creative Biolabs offers C1r proenzyme functional services, including detection of C1r proenzyme binding and other tailored functional services for our esteemed clients engaged in clinical and scientific research.

References

1. Batista, André F., et al. "The importance of complement-mediated immune signaling in Alzheimer’s disease pathogenesis." International Journal of Molecular Sciences 25.2 (2024): 817.
2. Gröbner, Rebekka, et al. "C1R mutations trigger constitutive complement 1 activation in periodontal Ehlers-Danlos syndrome." Frontiers in Immunology 10 (2019): 2537.
3. Distributed under Open Access license CC BY 4.0, without modification.