Crystallization (Comment) | Organism |
---|---|
to 2.7 A resolution. The shape of factor I is bilobal, with the heavy and light chains making up the two halves of a brick. The arrangement of the domains in the larger heavy-chain lobe forms a ring structure, with the N-terminal FIMAC domain contacting the C-terminal LDLRA domains. This contact is linked covalently by a disulfide bridge between Cys15 and Cys237. Mapping of disease-associated gene polymorphisms and mutations known to alter cofactor-assisted C3b/C4b cleavage by factor I onto the factor I structure implies allosteric regulation of light-chain activity by contact of the heavy chain. Modeling of the ternary complex of factor I, factor H, and C3b | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | factor I is in a proteolytically inactive form, it circulates in a zymogen-like state despite being fully processed to the mature sequence. This inactive form is maintained by the noncatalytic heavy-chain allosterically modulating activity of the light chain. Once the ternary complex of factor I, a cofactor and a substrate is formed, the allosteric inhibition is released, and factor I is oriented for cleavage | Homo sapiens |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Ca2+ | two Ca2+ ions per molecule are present, each bound to one of the LDLRA domains. Crystallization data | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
glycoprotein | the first GlcNAc residue of each of the six N-linked glycosylation sites is ordered and visible in the electron density, crystallization data | Homo sapiens |
Purification (Comment) | Organism |
---|---|
- |
Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
serum | - |
Homo sapiens | - |
General Information | Comment | Organism |
---|---|---|
physiological function | factor I is in a proteolytically inactive form, it circulates in a zymogen-like state despite being fully processed to the mature sequence. This inactive form is maintained by the noncatalytic heavy-chain allosterically modulating activity of the light chain. Once the ternary complex of factor I, a cofactor and a substrate is formed, the allosteric inhibition is released, and factor I is oriented for cleavage. General model for factor I regulation of complement predicts that binding of the cofactor to C3b produces a stable platform onto which the factor I can dock, binding of factor I releases the allosteric inhibitory effects of the heavy chain and induces remodeling of the zymogen-activation domain and the active site forms around the substrate loop for the primary cleavage event | Homo sapiens |