2uwn

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[[Image:2uwn.jpg|left|200px]]
[[Image:2uwn.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 2uwn |SIZE=350|CAPTION= <scene name='initialview01'>2uwn</scene>, resolution 2.35&Aring;
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The line below this paragraph, containing "STRUCTURE_2uwn", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+A'>AC1</scene>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SCR:SUCROSE+OCTASULFATE'>SCR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY=
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or leave the SCENE parameter empty for the default display.
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|GENE=
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-->
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|DOMAIN=
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{{STRUCTURE_2uwn| PDB=2uwn | SCENE= }}
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|RELATEDENTRY=[[2jgx|2JGX]], [[1fhc|1FHC]], [[2jgw|2JGW]], [[1kov|1KOV]], [[1haq|1HAQ]], [[2v8e|2V8E]], [[1hfh|1HFH]], [[2g7i|2G7I]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2uwn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2uwn OCA], [http://www.ebi.ac.uk/pdbsum/2uwn PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2uwn RCSB]</span>
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}}
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'''CRYSTAL STRUCTURE OF HUMAN COMPLEMENT FACTOR H, SCR DOMAINS 6-8 (H402 RISK VARIANT), IN COMPLEX WITH LIGAND.'''
'''CRYSTAL STRUCTURE OF HUMAN COMPLEMENT FACTOR H, SCR DOMAINS 6-8 (H402 RISK VARIANT), IN COMPLEX WITH LIGAND.'''
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[[Category: Tyrrell, J.]]
[[Category: Tyrrell, J.]]
[[Category: Uhrin, D.]]
[[Category: Uhrin, D.]]
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[[Category: age-related macular degeneration]]
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[[Category: Age-related macular degeneration]]
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[[Category: alternative splicing]]
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[[Category: Alternative splicing]]
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[[Category: complement]]
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[[Category: Complement]]
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[[Category: complement alternate pathway]]
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[[Category: Complement alternate pathway]]
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[[Category: disease mutation]]
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[[Category: Disease mutation]]
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[[Category: factor h]]
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[[Category: Factor h]]
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[[Category: glycoprotein]]
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[[Category: Glycoprotein]]
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[[Category: glycosaminoglycan]]
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[[Category: Glycosaminoglycan]]
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[[Category: immune response]]
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[[Category: Immune response]]
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[[Category: immune system]]
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[[Category: Immune system]]
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[[Category: innate immunity]]
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[[Category: Innate immunity]]
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[[Category: polymorphism]]
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[[Category: Polymorphism]]
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[[Category: sucrose octasulphate]]
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[[Category: Sucrose octasulphate]]
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[[Category: sushi]]
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[[Category: Sushi]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:40:36 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:05:30 2008''
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Revision as of 14:40, 4 May 2008

Image:2uwn.jpg

Template:STRUCTURE 2uwn

CRYSTAL STRUCTURE OF HUMAN COMPLEMENT FACTOR H, SCR DOMAINS 6-8 (H402 RISK VARIANT), IN COMPLEX WITH LIGAND.


Overview

Nearly 50 million people worldwide suffer from age-related macular degeneration (AMD), which causes severe loss of central vision. A single-nucleotide polymorphism in the gene for the complement regulator factor H (FH), which causes a Tyr-to-His substitution at position 402, is linked to approximately 50% of attributable risks for AMD. We present the crystal structure of the region of FH containing the polymorphic amino acid His402 in complex with an analogue of the glycosaminoglycans (GAGs) that localize the complement regulator on the cell surface. The structure demonstrates direct coordination of ligand by the disease-associated polymorphic residue, providing a molecular explanation of the genetic observation. This glycan-binding site occupies the center of an extended interaction groove on the regulator's surface, implying multivalent binding of sulfated GAGs. This finding is confirmed by structure-based site-directed mutagenesis, nuclear magnetic resonance-monitored binding experiments performed for both H402 and Y402 variants with this and another model GAG, and analysis of an extended GAG-FH complex.

About this Structure

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

Reference

Structural basis for complement factor H linked age-related macular degeneration., Prosser BE, Johnson S, Roversi P, Herbert AP, Blaum BS, Tyrrell J, Jowitt TA, Clark SJ, Tarelli E, Uhrin D, Barlow PN, Sim RB, Day AJ, Lea SM, J Exp Med. 2007 Oct 1;204(10):2277-83. Epub 2007 Sep 24. PMID:17893204 Page seeded by OCA on Sun May 4 17:40:36 2008

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