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| - | [[Image:1b68.gif|left|200px]] | + | {{Seed}} |
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| | {{STRUCTURE_1b68| PDB=1b68 | SCENE= }} | | {{STRUCTURE_1b68| PDB=1b68 | SCENE= }} |
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| - | '''APOLIPOPROTEIN E4 (APOE4), 22K FRAGMENT'''
| + | ===APOLIPOPROTEIN E4 (APOE4), 22K FRAGMENT=== |
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| - | ==Overview==
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| - | Apolipoprotein E (apoE) is an important lipid-transport protein in human plasma and brain. It has three common isoforms (apoE2, apoE3, and apoE4). ApoE is a major genetic risk factor in heart disease and in neurodegenerative disease, including Alzheimer's disease. The interaction of apoE with heparan sulfate proteoglycans plays an important role in lipoprotein remnant uptake and likely in atherogenesis and Alzheimer's disease. Here we report our studies of the interaction of the N-terminal domain of apoE4 (residues 1-191), which contains the major heparin-binding site, with an enzymatically prepared heparin oligosaccharide. Identified by its high affinity for the N-terminal domain of apoE4, this oligosaccharide was determined to be an octasaccharide of the structure DeltaUAp2S(1-->[4)-alpha-D-GlcNpS6S(1-->4)-alpha-L-IdoAp2S(1-->](3)4)-alph a-D-GlcNpS6S by nuclear magnetic resonance spectroscopy, capillary electrophoresis, and polyacrylamide gel electrophoresis. Kinetic analysis of the interaction between the N-terminal apoE4 fragment and immobilized heparin by surface plasmon resonance yielded a K(d) of 150 nM. A similar binding constant (K(d) = 140 nM) was observed for the interaction between immobilized N-terminal apoE4 and the octasaccharide. Isothermal titration calorimetry revealed a K(d) of 75 nM for the interaction of the N-terminal apoE fragment and the octasaccharide with a binding stoichiometry of approximately 1:1. Using previous studies and molecular modeling, we propose a binding site for this octasaccharide in a basic residue-rich region of helix 4 of the N-terminal fragment. From the X-ray crystal structure of the N-terminal apoE4, we predicted that binding of the octasaccharide at this site would result in a change in intrinsic fluorescence. This prediction was confirmed experimentally by an observed increase in fluorescence intensity with octasaccharide binding corresponding to a K(d) of approximately 1 microM.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_11258893}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 11258893 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_11258893}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Plasma protein]] | | [[Category: Plasma protein]] |
| | [[Category: Vldl]] | | [[Category: Vldl]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 11:07:18 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jun 30 18:21:31 2008'' |
Revision as of 15:21, 30 June 2008
Template:STRUCTURE 1b68
APOLIPOPROTEIN E4 (APOE4), 22K FRAGMENT
Template:ABSTRACT PUBMED 11258893
About this Structure
1B68 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Interaction of the N-terminal domain of apolipoprotein E4 with heparin., Dong J, Peters-Libeu CA, Weisgraber KH, Segelke BW, Rupp B, Capila I, Hernaiz MJ, LeBrun LA, Linhardt RJ, Biochemistry. 2001 Mar 6;40(9):2826-34. PMID:11258893
Page seeded by OCA on Mon Jun 30 18:21:31 2008
