2qfg: Difference between revisions

Revision as of 12:31, 23 January 2008

Solution Structure of the N-terminal SCR-1/5 fragment of Complement Factor H.

OverviewOverview

Factor H (FH) is a plasma glycoprotein that plays a central role in, regulation of the alternative pathway of complement. It is composed of 20, short complement regulator (SCR) domains. The SCR-1/5 fragment is required, for decay acceleration and cofactor activity, while the SCR-16/20 fragment, possesses binding sites for complement C3d and heparin. X-ray scattering, and analytical ultracentrifugation showed that SCR-1/5 was monomeric, while SCR-16/20 formed dimers. The Guinier radius of gyration R(G) of 4.3, nm for SCR-1/5 and those of 4.7 nm and about 7.8 nm for monomeric and, dimeric SCR-16/20, respectively, showed that their structures are, partially folded back and bent. The distance distribution function P(r), showed that SCR-1/5 has a maximum dimension of 15 nm while monomeric and, dimeric SCR-16/20 are 17 nm and about 27 nm long, respectively. The, sedimentation coefficient of 2.4 S for SCR-1/5 showed no, concentration-dependence, while that for SCR-16/20 was 2.8 S for the, monomer and 3.9 S for the dimer. Sedimentation equilibrium data showed, that SCR-1/5 is monomeric while SCR-16/20 exhibited a weak monomer-dimer, equilibrium with a dissociation constant of 16 microM. The constrained, scattering and sedimentation modelling of SCR-1/5 and SCR-16/20 showed, that partially folded-back and bent flexible SCR arrangements fitted both, data sets better than extended linear arrangements, and that the dimer was, best modelled in the SCR-16/20 model by an end-to-end association of two, SCR-20 domains. The SCR-1/5 and SCR-16/20 models were conformationally, similar to the previously determined partially folded-back structure for, intact wild-type FH, hence suggesting a partial explanation of the intact, FH structure. Comparison of the SCR-16/20 model with the crystal structure, of C3b clarified reasons for the distribution of mutations leading to, atypical haemolytic uraemic syndrome.

About this StructureAbout this Structure

2QFG is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

The regulatory SCR-1/5 and cell surface-binding SCR-16/20 fragments of factor H reveal partially folded-back solution structures and different self-associative properties., Okemefuna AI, Gilbert HE, Griggs KM, Ormsby RJ, Gordon DL, Perkins SJ, J Mol Biol. 2008 Jan 4;375(1):80-101. Epub 2007 Sep 14. PMID:18005991

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OCA

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-[[Image:2qfg.gif|left|200px]]<br />
+[[Image:2qfg.jpg|left|200px]]<br /><applet load="2qfg" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="2qfg" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="2qfg" />
 '''Solution Structure of the N-terminal SCR-1/5 fragment of Complement Factor H.'''<br />
-==Disease==
+==Overview==
-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]]
+Factor H (FH) is a plasma glycoprotein that plays a central role in, regulation of the alternative pathway of complement. It is composed of 20, short complement regulator (SCR) domains. The SCR-1/5 fragment is required, for decay acceleration and cofactor activity, while the SCR-16/20 fragment, possesses binding sites for complement C3d and heparin. X-ray scattering, and analytical ultracentrifugation showed that SCR-1/5 was monomeric, while SCR-16/20 formed dimers. The Guinier radius of gyration R(G) of 4.3, nm for SCR-1/5 and those of 4.7 nm and about 7.8 nm for monomeric and, dimeric SCR-16/20, respectively, showed that their structures are, partially folded back and bent. The distance distribution function P(r), showed that SCR-1/5 has a maximum dimension of 15 nm while monomeric and, dimeric SCR-16/20 are 17 nm and about 27 nm long, respectively. The, sedimentation coefficient of 2.4 S for SCR-1/5 showed no, concentration-dependence, while that for SCR-16/20 was 2.8 S for the, monomer and 3.9 S for the dimer. Sedimentation equilibrium data showed, that SCR-1/5 is monomeric while SCR-16/20 exhibited a weak monomer-dimer, equilibrium with a dissociation constant of 16 microM. The constrained, scattering and sedimentation modelling of SCR-1/5 and SCR-16/20 showed, that partially folded-back and bent flexible SCR arrangements fitted both, data sets better than extended linear arrangements, and that the dimer was, best modelled in the SCR-16/20 model by an end-to-end association of two, SCR-20 domains. The SCR-1/5 and SCR-16/20 models were conformationally, similar to the previously determined partially folded-back structure for, intact wild-type FH, hence suggesting a partial explanation of the intact, FH structure. Comparison of the SCR-16/20 model with the crystal structure, of C3b clarified reasons for the distribution of mutations leading to, atypical haemolytic uraemic syndrome.
 ==About this Structure==
-QFG 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2QFG OCA].
+QFG 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=2QFG OCA].
+==Reference==
+The regulatory SCR-1/5 and cell surface-binding SCR-16/20 fragments of factor H reveal partially folded-back solution structures and different self-associative properties., Okemefuna AI, Gilbert HE, Griggs KM, Ormsby RJ, Gordon DL, Perkins SJ, J Mol Biol. 2008 Jan 4;375(1):80-101. Epub 2007 Sep 14. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18005991 18005991]
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
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 [[Category: x-ray scattering]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:32:47 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 11:31:33 2008''