Literature summary for 3.4.21.45 extracted from

Roversi, P.; Johnson, S.; Caesar, J.J.; McLean, F.; Leath, K.J.; Tsiftsoglou, S.A.; Morgan, B.P.; Harris, C.L.; Sim, R.B.; Lea, S.M.
Structural basis for complement factor I control and its disease-associated sequence polymorphisms (2011), Proc. Natl. Acad. Sci. USA, 108, 12839-12844.

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Crystallization (Commentary)

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

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

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

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

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Posttranslational Modification

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 (Commentary)

Purification (Comment)	Organism
-	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
serum	-	Homo sapiens	-

General Information

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