View source for 1hfi


==SOLUTION STRUCTURE OF A PAIR OF COMPLEMENT MODULES BY NUCLEAR MAGNETIC RESONANCE==
<StructureSection load='1hfi' size='340' side='right'caption='[[1hfi]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1hfi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HFI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HFI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 1 model</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hfi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hfi OCA], [https://pdbe.org/1hfi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hfi RCSB], [https://www.ebi.ac.uk/pdbsum/1hfi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hfi ProSAT]</span></td></tr>
</table>
== Disease ==
[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/hf/1hfi_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1hfi ConSurf].
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== Publication Abstract from PubMed ==
A portion of human complement factor H spanning the 15th (H15) and 16th (H16) of its 20 modules, has been expressed in a yeast vector and subjected to structure determination in solution using two-dimensional 1H-NMR. The structure of H15 is very similar to that already established for the fifth module of factor H and H16, consistent with the view that all such complement control (C-) modules share a common overall topology. In addition, the tertiary structures of the component modules of the H15-16 pair are very similar to those of the modules when expressed individually, implying that each folds entirely autonomously within intact factor H. Aromatic residues in the third turn of H15 and the second turn of H16, together with a leucine residue from the linker region, contribute to a small intermodular interface. Comparatively few nuclear Overhauser effects were observable between protons on different modules. Consequently, a wide range of angles of "twist" (131 (+/- 146) degrees, mean value (+/- 1 standard deviation)), i.e. rotation about the long axis of one module with respect to the other, exists in the family of structures generated on the basis of the experimental data. However, much smaller variations occur in the two, orthogonal, angles (175 (+/- 12) degrees and 103 (+/- 6) degrees) that describe the "tilt". These observations may suggest upper limits on the relative flexibility of the two modules. Models were built to assess the outcome of applying such restrictions to all the neighbours within a string of 20 C-modules, and the resulting structures compare well with factor H as visualized by electron microscopy.

Solution structure of a pair of complement modules by nuclear magnetic resonance.,Barlow PN, Steinkasserer A, Norman DG, Kieffer B, Wiles AP, Sim RB, Campbell ID J Mol Biol. 1993 Jul 5;232(1):268-84. PMID:8331663<ref>PMID:8331663</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1hfi" style="background-color:#fffaf0;"></div>

==See Also==
*[[Complement factor 3D structures|Complement factor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Barlow PN]]
[[Category: Campbell ID]]
[[Category: Kieffer B]]
[[Category: Norman DG]]
[[Category: Sim RB]]
[[Category: Steinkasserer A]]
[[Category: Wiles AP]]