2BZM
Solution structure of the primary host recognition region of complement factor H
Summary for 2BZM
| Entry DOI | 10.2210/pdb2bzm/pdb |
| Related | 1FHC 1HAQ 1HCC 1HFH 1HFI 1KOV |
| Descriptor | COMPLEMENT FACTOR H (1 entity in total) |
| Functional Keywords | immune system, factor h, complement, hus, heparin, polyanions, immune response, innate immunity, complement alternate pathway |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Secreted: P08603 |
| Total number of polymer chains | 1 |
| Total formula weight | 14773.79 |
| Authors | Herbert, A.P.,Uhrin, D.,Lyon, M.,Pangburn, M.K.,Barlow, P.N. (deposition date: 2005-08-18, release date: 2006-03-22, Last modification date: 2024-11-20) |
| Primary citation | Herbert, A.P.,Uhrin, D.,Lyon, M.,Pangburn, M.K.,Barlow, P.N. Disease-Associated Sequence Variations Congregate in a Polyanion Recognition Patch on Human Factor H Revealed in Three-Dimensional Structure. J.Biol.Chem., 281:16512-, 2006 Cited by PubMed Abstract: Mutations and polymorphisms in the regulator of complement activation, factor H, have been linked to atypical hemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis, and age-related macular degeneration. Many aHUS patients carry mutations in the two C-terminal modules of factor H, which normally confer upon this abundant 155-kDa plasma glycoprotein its ability to selectively bind self-surfaces and prevent them from inappropriately triggering the complement cascade via the alternative pathway. In the current study, the three-dimensional solution structure of the C-terminal module pair of factor H has been determined. A binding site for a fully sulfated heparin-derived tetrasaccharide has been delineated using chemical shift mapping and the C3d/C3b-binding site inferred from sequence comparisons and computational docking. The resultant information allows assessment of the likely consequences of aHUS-associated amino acid substitutions in this critical region of factor H. It is striking that, excepting those likely to perturb the three-dimensional structure, aHUS-associated missense mutations congregate in the polyanion-binding site delineated in this study, thus potentially disrupting a vital mechanism for control of complement on self-surfaces in the microvasculature of the kidney. It is intriguing that a single nucleotide polymorphism predisposing to age-related macular degeneration occupies another region of factor H that harbors a polyanion-binding site. PubMed: 16533809DOI: 10.1074/JBC.M513611200 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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