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2bzm
From Proteopedia
(New page: 200px<br /> <applet load="2bzm" size="450" color="white" frame="true" align="right" spinBox="true" caption="2bzm" /> '''SOLUTION STRUCTURE OF THE PRIMARY HOST RECO...) |
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| - | [[Image:2bzm.gif|left|200px]]<br /> | + | [[Image:2bzm.gif|left|200px]]<br /><applet load="2bzm" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2bzm" size=" | + | |
caption="2bzm" /> | caption="2bzm" /> | ||
'''SOLUTION STRUCTURE OF THE PRIMARY HOST RECOGNITION REGION OF COMPLEMENT FACTOR H'''<br /> | '''SOLUTION STRUCTURE OF THE PRIMARY HOST RECOGNITION REGION OF COMPLEMENT FACTOR H'''<br /> | ||
==Overview== | ==Overview== | ||
| - | 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 | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2BZM 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:// | + | 2BZM 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=2BZM OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Barlow, P | + | [[Category: Barlow, P N.]] |
| - | [[Category: Herbert, A | + | [[Category: Herbert, A P.]] |
[[Category: Lyon, M.]] | [[Category: Lyon, M.]] | ||
| - | [[Category: Pangburn, M | + | [[Category: Pangburn, M K.]] |
[[Category: Uhrin, D.]] | [[Category: Uhrin, D.]] | ||
[[Category: complement]] | [[Category: complement]] | ||
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[[Category: polyanions]] | [[Category: polyanions]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:43:20 2008'' |
Revision as of 14:43, 21 February 2008
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SOLUTION STRUCTURE OF THE PRIMARY HOST RECOGNITION REGION OF COMPLEMENT FACTOR H
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Complement factor H deficiency OMIM:[134370], Factor H and factor H-like 1 OMIM:[134370], Hemolytic-uremic syndrome OMIM:[134370], Macular degeneration, age-related, 4 OMIM:[134370], Membranoproliferative glomerulonephritis with CFH deficiency OMIM:[134370]
About this Structure
2BZM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Disease-associated sequence variations congregate in a polyanion recognition patch on human factor H revealed in three-dimensional structure., Herbert AP, Uhrin D, Lyon M, Pangburn MK, Barlow PN, J Biol Chem. 2006 Jun 16;281(24):16512-20. Epub 2006 Mar 13. PMID:16533809
Page seeded by OCA on Thu Feb 21 16:43:20 2008
