Abstract |
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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Authors | L M Dong, S Parkin, S D Trakhanov, B Rupp, T Simmons, K S Arnold, Y M Newhouse, T L Innerarity, K H Weisgraber |
Journal | Nature structural biology
(Nat Struct Biol)
Vol. 3
Issue 8
Pg. 718-22
(Aug 1996)
ISSN: 1072-8368 [Print] United States |
PMID | 8756331
(Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Apolipoprotein E2
- Apolipoproteins E
- Peptide Fragments
- Receptors, LDL
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Topics |
- Apolipoprotein E2
- Apolipoproteins E
(chemistry, genetics, metabolism)
- Crystallography, X-Ray
- Humans
- Hyperlipoproteinemia Type III
(genetics, metabolism)
- Models, Molecular
- Peptide Fragments
(chemistry, genetics, metabolism)
- Protein Binding
- Protein Structure, Secondary
- Receptors, LDL
(chemistry, metabolism)
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