2ic4
From Proteopedia
(New page: 200px<br /> <applet load="2ic4" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ic4" /> '''Solution structure of the His402 allotype o...) |
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'''Solution structure of the His402 allotype of the Factor H SCR6-SCR7-SCR8 fragment'''<br /> | '''Solution structure of the His402 allotype of the Factor H SCR6-SCR7-SCR8 fragment'''<br /> | ||
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==Overview== | ==Overview== | ||
Factor H (FH) is a major complement control protein in serum. The seventh, short complement regulator (SCR-7) domain of the 20 in FH is associated, with age-related macular degeneration through a Tyr402His polymorphism., The recombinant SCR-6/8 domains containing either His402 or Tyr402 and, their complexes with a heparin decasaccharide were studied by analytical, ultracentrifugation and X-ray scattering. The sedimentation coefficient is, concentration dependent, giving a value of 2.0 S at zero concentration and, a frictional ratio f/f(o) of 1.2 for both allotypes. The His402 allotype, showed a slightly greater self-association than the Tyr402 allotype, and, small amounts of dimeric SCR-6/8 were found for both allotypes in 50 mM, 137 mM and 250 mM NaCl buffers. Sedimentation equilibrium data were, interpreted in terms of a monomer-dimer equilibrium with a dissociation, constant of 40 muM for the His402 form. The Guinier radius of gyration, R(G) of 3.1-3.3 nm and the R(G)/R(O) ratio of 2.0-2.1 showed that SCR-6/8, is relatively extended in solution. The distance distribution function, P(r) showed a maximum dimension of 10 nm, which is less than the length, expected for a linear domain arrangement. The constrained scattering and, sedimentation modelling of FH SCR-6/8 showed that bent SCR arrangements, fit the data better than linear arrangements. Previously identified, heparin-binding residues were exposed on the outside curvature of this, bent domain structure. Heparin caused the formation of a more linear, structure, possibly by binding to residues in the linker. It was concluded, that the His402 allotype may self-associate more readily than the Tyr402, allotype, SCR-6/8 is partly responsible for the folded-back structure of, intact FH, and SCR-6/8 changes conformation upon heparin binding. | Factor H (FH) is a major complement control protein in serum. The seventh, short complement regulator (SCR-7) domain of the 20 in FH is associated, with age-related macular degeneration through a Tyr402His polymorphism., The recombinant SCR-6/8 domains containing either His402 or Tyr402 and, their complexes with a heparin decasaccharide were studied by analytical, ultracentrifugation and X-ray scattering. The sedimentation coefficient is, concentration dependent, giving a value of 2.0 S at zero concentration and, a frictional ratio f/f(o) of 1.2 for both allotypes. The His402 allotype, showed a slightly greater self-association than the Tyr402 allotype, and, small amounts of dimeric SCR-6/8 were found for both allotypes in 50 mM, 137 mM and 250 mM NaCl buffers. Sedimentation equilibrium data were, interpreted in terms of a monomer-dimer equilibrium with a dissociation, constant of 40 muM for the His402 form. The Guinier radius of gyration, R(G) of 3.1-3.3 nm and the R(G)/R(O) ratio of 2.0-2.1 showed that SCR-6/8, is relatively extended in solution. The distance distribution function, P(r) showed a maximum dimension of 10 nm, which is less than the length, expected for a linear domain arrangement. The constrained scattering and, sedimentation modelling of FH SCR-6/8 showed that bent SCR arrangements, fit the data better than linear arrangements. Previously identified, heparin-binding residues were exposed on the outside curvature of this, bent domain structure. Heparin caused the formation of a more linear, structure, possibly by binding to residues in the linker. It was concluded, that the His402 allotype may self-associate more readily than the Tyr402, allotype, SCR-6/8 is partly responsible for the folded-back structure of, intact FH, and SCR-6/8 changes conformation upon heparin binding. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Complement factor H deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134370 134370]], Factor H and factor H-like 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134370 134370]], Hemolytic-uremic syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134370 134370]], Macular degeneration, age-related, 4 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134370 134370]], Membranoproliferative glomerulonephritis with CFH deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=134370 134370]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2IC4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2IC4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IC4 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: x-ray scattering]] | [[Category: x-ray scattering]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:30:49 2008'' |
Revision as of 13:30, 23 January 2008
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Solution structure of the His402 allotype of the Factor H SCR6-SCR7-SCR8 fragment
Overview
Factor H (FH) is a major complement control protein in serum. The seventh, short complement regulator (SCR-7) domain of the 20 in FH is associated, with age-related macular degeneration through a Tyr402His polymorphism., The recombinant SCR-6/8 domains containing either His402 or Tyr402 and, their complexes with a heparin decasaccharide were studied by analytical, ultracentrifugation and X-ray scattering. The sedimentation coefficient is, concentration dependent, giving a value of 2.0 S at zero concentration and, a frictional ratio f/f(o) of 1.2 for both allotypes. The His402 allotype, showed a slightly greater self-association than the Tyr402 allotype, and, small amounts of dimeric SCR-6/8 were found for both allotypes in 50 mM, 137 mM and 250 mM NaCl buffers. Sedimentation equilibrium data were, interpreted in terms of a monomer-dimer equilibrium with a dissociation, constant of 40 muM for the His402 form. The Guinier radius of gyration, R(G) of 3.1-3.3 nm and the R(G)/R(O) ratio of 2.0-2.1 showed that SCR-6/8, is relatively extended in solution. The distance distribution function, P(r) showed a maximum dimension of 10 nm, which is less than the length, expected for a linear domain arrangement. The constrained scattering and, sedimentation modelling of FH SCR-6/8 showed that bent SCR arrangements, fit the data better than linear arrangements. Previously identified, heparin-binding residues were exposed on the outside curvature of this, bent domain structure. Heparin caused the formation of a more linear, structure, possibly by binding to residues in the linker. It was concluded, that the His402 allotype may self-associate more readily than the Tyr402, allotype, SCR-6/8 is partly responsible for the folded-back structure of, intact FH, and SCR-6/8 changes conformation upon heparin binding.
About this Structure
2IC4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Associative and Structural Properties of the Region of Complement Factor H Encompassing the Tyr402His Disease-related Polymorphism and its Interactions with Heparin., Fernando AN, Furtado PB, Clark SJ, Gilbert HE, Day AJ, Sim RB, Perkins SJ, J Mol Biol. 2007 Apr 27;368(2):564-81. Epub 2007 Feb 22. PMID:17362990
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