2qfh: Difference between revisions

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-[[Image:2qfh.jpg|left|200px]]
- {{Structure
+==Solution Structure of the C-terminal SCR-16/20 fragment of Complement Factor H.==
-|PDB= 2qfh |SIZE=350|CAPTION= <scene name='initialview01'>2qfh</scene>
+<StructureSection load='2qfh' size='340' side='right'caption='[[2qfh]]' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND=
+<table><tr><td colspan='2'>[[2qfh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QFH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QFH FirstGlance]. <br>
-|ACTIVITY=
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray solution scattering</td></tr>
-|GENE= CFH, HF, HF1, HF2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qfh OCA], [https://pdbe.org/2qfh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qfh RCSB], [https://www.ebi.ac.uk/pdbsum/2qfh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qfh ProSAT]</span></td></tr>
-|DOMAIN=
+</table>
-|RELATEDENTRY=[[1hcc|1HCC]], [[2g7i|2G7I]], [[1haq|1HAQ]], [[2qfg|2QFG]]
+== Disease ==
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qfh OCA], [http://www.ebi.ac.uk/pdbsum/2qfh PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2qfh RCSB]</span>
+[https://www.uniprot.org/uniprot/CFAH_HUMAN CFAH_HUMAN] Genetic variations in CFH are associated with basal laminar drusen (BLD) [MIM:[https://omim.org/entry/126700 126700]; also known as drusen of Bruch membrane or cuticular drusen or grouped early adult-onset drusen. Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. Basal laminar drusen refers to an early adult-onset drusen phenotype that shows a pattern of uniform small, slightly raised yellow subretinal nodules randomly scattered in the macula. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss.  Defects in CFH are the cause of complement factor H deficiency (CFHD) [MIM:[https://omim.org/entry/609814 609814]. A disorder that can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. Laboratory features usually include decreased serum levels of factor H, complement component C3, and a decrease in other terminal complement components, indicating activation of the alternative complement pathway. It is associated with a number of renal diseases with variable clinical presentation and progression, including membranoproliferative glomerulonephritis and atypical hemolytic uremic syndrome.<ref>PMID:9312129</ref> <ref>PMID:10803850</ref> <ref>PMID:11170895</ref> <ref>PMID:11170896</ref> <ref>PMID:11158219</ref> <ref>PMID:12020532</ref> <ref>PMID:14978182</ref> <ref>PMID:16612335</ref>   Defects in CFH are a cause of susceptibility to hemolytic uremic syndrome atypical type 1 (AHUS1) [MIM:[https://omim.org/entry/235400 235400]. An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Note=Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.<ref>PMID:14978182</ref> <ref>PMID:9551389</ref> <ref>PMID:10577907</ref> <ref>PMID:10762557</ref> <ref>PMID:11851332</ref> <ref>PMID:14583443</ref> <ref>PMID:12960213</ref> <ref>PMID:20513133</ref>   Genetic variation in CFH is associated with age-related macular degeneration type 4 (ARMD4) [MIM:[https://omim.org/entry/610698 610698]. ARMD is a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid (known as drusen) that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.<ref>PMID:22019782</ref>
-}}
+== Function ==
+[https://www.uniprot.org/uniprot/CFAH_HUMAN CFAH_HUMAN] Factor H functions as a cofactor in the inactivation of C3b by factor I and also increases the rate of dissociation of the C3bBb complex (C3 convertase) and the (C3b)NBB complex (C5 convertase) in the alternative complement pathway.
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/qf/2qfh_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2qfh ConSurf].
+<div style="clear:both"></div>
-'''Solution Structure of the C-terminal SCR-16/20 fragment of Complement Factor H.'''
+==See Also==
+*[[Complement factor 3D structures|Complement factor 3D structures]]
+== References ==
-==Overview==
+<references/>
-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.
+__TOC__
+</StructureSection>
-==About this Structure==
-QFH is a [[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=2QFH 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://www.ncbi.nlm.nih.gov/pubmed/18005991 18005991]
 [[Category: Homo sapiens]]
-[[Category: Single protein]]
+[[Category: Large Structures]]
-[[Category: Gilbert, H E.]]
+[[Category: Gilbert HE]]
-[[Category: Gordon, D L.]]
+[[Category: Gordon DL]]
-[[Category: Griggs, K M.]]
+[[Category: Griggs KM]]
-[[Category: Okemefuna, A I.]]
+[[Category: Okemefuna AI]]
-[[Category: Ormsby, R J.]]
+[[Category: Ormsby RJ]]
-[[Category: Perkins, S J.]]
+[[Category: Perkins SJ]]
-[[Category: age-related macular degeneration]]
-[[Category: alternative splicing]]
-[[Category: complement]]
-[[Category: complement alternate pathway]]
-[[Category: disease mutation]]
-[[Category: factor h]]
-[[Category: glycoprotein]]
-[[Category: immune response]]
-[[Category: immune system]]
-[[Category: innate immunity]]
-[[Category: polymorphism]]
-[[Category: scr domain]]
-[[Category: sushi]]
-[[Category: x-ray scattering]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:48:44 2008''