C1rcontaining

C1r-containing refers to proteins or protein complexes that include the C1r component of the classical complement pathway. The best-known example is the C1 complex, a multi-subunit protease assembly that also contains C1q and C1s. In the activated state the C1 complex is often described as C1q bound to a C1r2C1s2 tetramer, forming a hexameric arrangement in which six C1q heads recruit two C1r and two C1s proteases.

C1r and C1s are serine proteases that exist as zymogens in the resting complex. Activation proceeds in two steps: first, upon binding of C1q to the Fc regions of antibodies within immune complexes, C1r undergoes autoproteolytic activation. Activated C1r then cleaves and activates C1s, and active C1s cleaves the downstream targets C4 and C2 to generate the C3 convertase C4b2a, initiating the classical complement cascade.

Regulation of C1r-containing activity is essential to prevent unintended inflammation. C1 inhibitor (C1-INH) rapidly inactivates activated C1r and C1s, dampening the cascade and maintaining homeostasis. Deficiencies or dysfunction in C1-INH or other components of the C1 complex can contribute to immune dysregulation, autoimmune phenomena, or hereditary angioedema in humans.

In research contexts, the term C1r-containing is used to describe proteins or complexes that include the C1r protease as part of their structure or function, particularly within studies of the classical pathway, its regulation, and related pathological conditions.