1nfo
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= E2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= E2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1nfo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nfo OCA], [http://www.ebi.ac.uk/pdbsum/1nfo PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1nfo RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
The defective binding of apolipoprotein (apo) E2 to lipoprotein receptors, an underlying cause of type III hyperlipoproteinemia, results from replacement of Arg 158 with Cys, disrupting the naturally occurring salt bridge between Asp 154 and Arg 158. A new bond between Asp 154 and Arg 150 is formed, shifting Arg 150 out of the receptor binding region. Elimination of the 154-150 salt bridge by site-directed mutagenesis of Asp 154 to Ala restored the receptor binding activity to near normal levels. The X-ray crystal structure of apoE2 Ala 154 demonstrated that Arg 150 was relocated within the receptor binding region. Our results demonstrate that defective binding of apoE2 occurs by a novel mechanism of the replacement of one salt bridge with another. | The defective binding of apolipoprotein (apo) E2 to lipoprotein receptors, an underlying cause of type III hyperlipoproteinemia, results from replacement of Arg 158 with Cys, disrupting the naturally occurring salt bridge between Asp 154 and Arg 158. A new bond between Asp 154 and Arg 150 is formed, shifting Arg 150 out of the receptor binding region. Elimination of the 154-150 salt bridge by site-directed mutagenesis of Asp 154 to Ala restored the receptor binding activity to near normal levels. The X-ray crystal structure of apoE2 Ala 154 demonstrated that Arg 150 was relocated within the receptor binding region. Our results demonstrate that defective binding of apoE2 occurs by a novel mechanism of the replacement of one salt bridge with another. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Alzheimer disease-2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107741 107741]], Hyperlipoproteinemia, type III OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107741 107741]], Lipoprotein glomerulopathy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107741 107741]], Macular degeneration, age-related OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107741 107741]], Myocardial infarction susceptibility OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107741 107741]], Sea-blue histiocyte disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=107741 107741]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: vldl]] | [[Category: vldl]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:29:40 2008'' |
Revision as of 19:29, 30 March 2008
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| , resolution 2.0Å | |||||||
|---|---|---|---|---|---|---|---|
| Gene: | E2 (Homo sapiens) | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
APOLIPOPROTEIN E2 (APOE2, D154A MUTATION)
Overview
The defective binding of apolipoprotein (apo) E2 to lipoprotein receptors, an underlying cause of type III hyperlipoproteinemia, results from replacement of Arg 158 with Cys, disrupting the naturally occurring salt bridge between Asp 154 and Arg 158. A new bond between Asp 154 and Arg 150 is formed, shifting Arg 150 out of the receptor binding region. Elimination of the 154-150 salt bridge by site-directed mutagenesis of Asp 154 to Ala restored the receptor binding activity to near normal levels. The X-ray crystal structure of apoE2 Ala 154 demonstrated that Arg 150 was relocated within the receptor binding region. Our results demonstrate that defective binding of apoE2 occurs by a novel mechanism of the replacement of one salt bridge with another.
About this Structure
1NFO is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Novel mechanism for defective receptor binding of apolipoprotein E2 in type III hyperlipoproteinemia., Dong LM, Parkin S, Trakhanov SD, Rupp B, Simmons T, Arnold KS, Newhouse YM, Innerarity TL, Weisgraber KH, Nat Struct Biol. 1996 Aug;3(8):718-22. PMID:8756331
Page seeded by OCA on Sun Mar 30 22:29:40 2008
