2ic4: Difference between revisions
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{{STRUCTURE_2ic4| PDB=2ic4 | SCENE= }} | |||
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'''Solution structure of the His402 allotype of the Factor H SCR6-SCR7-SCR8 fragment''' | '''Solution structure of the His402 allotype of the Factor H SCR6-SCR7-SCR8 fragment''' | ||
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[[Category: Perkins, S J.]] | [[Category: Perkins, S J.]] | ||
[[Category: Sim, R B.]] | [[Category: Sim, R B.]] | ||
[[Category: | [[Category: Factor h]] | ||
[[Category: | [[Category: Homology modelling]] | ||
[[Category: | [[Category: Ultracentrifugation]] | ||
[[Category: | [[Category: X-ray scattering]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:19:08 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 07:19, 4 May 2008
Solution structure of the His402 allotype of the Factor H SCR6-SCR7-SCR8 fragment
OverviewOverview
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 microM 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 StructureAbout this Structure
2IC4 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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 Page seeded by OCA on Sun May 4 07:19:08 2008