2000
DOI: 10.4049/jimmunol.165.4.2048
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The Cleavage of Two C1s Subunits by a Single Active C1r Reveals Substantial Flexibility of the C1s-C1r-C1r-C1s Tetramer in the C1 Complex

Abstract: The activation of the C1s-C1r-C1r-C1s tetramer in the C1 complex, which involves the cleavage of an Arg-Ile bond in the catalytic domains of the subcomponents, is a two-step process. First, the autolytic activation of C1r takes place, then activated C1r cleaves zymogen C1s. The Arg463Gln mutant of C1r (C1rQI) is stabilized in the zymogen form. This mutant was used to form a C1q-(C1s-C1rQI-C1r-C1s) heteropentamer to study the relative position of the C1r and C1s subunits in the C1 complex. After triggering the … Show more

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Cited by 8 publications
(5 citation statements)
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“…We should keep in mind that we are dealing with fluid phase reactions in our present study. However, inside the C1 complex the catalytic domains of C1r and C1s are precisely positioned; therefore, the efficiency of C1s cleavage by the C1r dimer can be significantly higher (31).…”
Section: Discussionmentioning
confidence: 99%
“…We should keep in mind that we are dealing with fluid phase reactions in our present study. However, inside the C1 complex the catalytic domains of C1r and C1s are precisely positioned; therefore, the efficiency of C1s cleavage by the C1r dimer can be significantly higher (31).…”
Section: Discussionmentioning
confidence: 99%
“…C1, the first component of the classical complement cascade, is a multimolecular complex composed of the protein C1q, and the catalytic subunit C1s-C1r-C1r-C1s, the latter of which is a calciumdependent tetramer composed of two different serine proteases (107,108) (Fig. 3).…”
Section: Cerebral Ischemia and Complement: Stroke Modelsmentioning
confidence: 99%
“…Serum components, such as the complement system, consist of 35 or more soluble protein and cell surface receptors/regulators that interact with pathogen structures and activate a cascade of proteases that eliminate invading parasites, and this system comprises the first line of defense [16,[43][44][45]. Briefly, the action of the classical pathway is mediated by the antibodies binding to pathogen antigens, then the antibodies interact with the complement C1 protein, and it cleaves C2 and C4 to generate C2a and C4b, which join to the pathogen surface and form the C3 convertase C4b2a [16,46]. Lectin complement pathway is the first to recognize T. cruzi; this is active by the binding of ficolins to the carbohydrates on the parasite surface and also mannan-binding lectins (MBLs) to the mannan on the surface of the parasite; then cysteine proteases bound to these molecules and cleave C2 and C4 and; this event also generates the C3 convertase C4b2a [47][48][49].…”
Section: Complement Evasionmentioning
confidence: 99%