2xrc

Human complement factor I

spinqualitylabelsall models 2xrc, resolution 2.69Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xrc is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.69Å Ligands: CA, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CFAI_HUMAN HELLP syndrome;Immunodeficiency with factor I anomaly;De novo thrombotic microangiopathy after kidney transplantation;Atypical hemolytic-uremic syndrome with I factor anomaly;Age-related macular degeneration. Disease susceptibility is associated with variations affecting the gene represented in this entry. Other genes may play a role in modifying the phenotype. The disease is caused by mutations affecting the gene represented in this entry. Disease susceptibility is associated with variations affecting the gene represented in this entry. Function CFAI_HUMAN Responsible for cleaving the alpha-chains of C4b and C3b in the presence of the cofactors C4-binding protein and factor H respectively. Publication Abstract from PubMed The complement system is a key component of innate and adaptive immune responses. Complement regulation is critical for prevention and control of disease. We have determined the crystal structure of the complement regulatory enzyme human factor I (fI). FI is in a proteolytically inactive form, demonstrating that it circulates in a zymogen-like state despite being fully processed to the mature sequence. Mapping of functional data from mutants of fI onto the structure suggests that this inactive form is maintained by the noncatalytic heavy-chain allosterically modulating activity of the light chain. Once the ternary complex of fI, a cofactor and a substrate is formed, the allosteric inhibition is released, and fI is oriented for cleavage. In addition to explaining how circulating fI is limited to cleaving only C3b/C4b, our model explains the molecular basis of disease-associated polymorphisms in fI and its cofactors. Structural basis for complement factor I control and its disease-associated sequence polymorphisms.,Roversi P, Johnson S, Caesar JJ, McLean F, Leath KJ, Tsiftsoglou SA, Morgan BP, Harris CL, Sim RB, Lea SM Proc Natl Acad Sci U S A. 2011 Aug 2;108(31):12839-44. Epub 2011 Jul 18. PMID:21768352 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Complement factor 3D structures

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