2v8e: Difference between revisions

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.

2V8E is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SCR, CL, SO4 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: 1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2V8E OCA].  

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