Three-dimensional structure of a cysteine-rich repeat from the low-density lipoprotein receptor

Daly, Norelle L., Scanlon, Martin J., Djordjevic, Julianne T., Kroon, Paulus A. and Smith, Ross (1995) Three-dimensional structure of a cysteine-rich repeat from the low-density lipoprotein receptor. Proceedings of the National Academy of Sciences, 92 14: 6334-6338. doi:10.1073/pnas.92.14.6334

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Author Daly, Norelle L.
Scanlon, Martin J.
Djordjevic, Julianne T.
Kroon, Paulus A.
Smith, Ross
Title Three-dimensional structure of a cysteine-rich repeat from the low-density lipoprotein receptor
Journal name Proceedings of the National Academy of Sciences   Check publisher's open access policy
ISSN 0027-8424
Publication date 1995-07-01
Sub-type Article (original research)
DOI 10.1073/pnas.92.14.6334
Open Access Status File (Publisher version)
Volume 92
Issue 14
Start page 6334
End page 6338
Total pages 5
Place of publication Washington, DC, United States
Publisher National Academy of Sciences
Language eng
Abstract The low-density lipoprotein (LDL) receptor plays a central rule in mammalian cholesterol metabolism, clearing lipoproteins which bear apolipoproteins E and B-100 from plasma. Mutations in this molecule are associated with familial hypercholesterolemia, a condition which leads to an elevated plasma cholesterol concentration and accelerated atherosclerosis. The N-terminal segment of the LDL receptor contains a heptad of cysteine- rich repeats that bind the lipoproteins. Similar repeats are present in related receptors, including the very low-density lipoprotein receptor and the LDL receptor-related protein/α2-macroglobulin receptor, and in proteins which are functionally unrelated, such as the C9 component of complement. The first repeat of the human LDL receptor has been expressed in Escherichia coli as a glutathione S-transferase fusion protein, and the cleaved and purified receptor module has been shown tn fold to a single, fully oxidized form that is recognized by the monoclonal antibody IgG-C7 in the presence of calcium ions. The three-dimensional structure of this module has been determined by two-dimensional NMR spectroscopy and shown to consist of a β-hairpin structure, followed by a series of β turns. Many of the side chains of the acidic residues, including the highly conserved Ser-Asp-Glu triad, are clustered on one face of the module. To our knowledge, this structure has not previously been described in any other protein and may represent a structural paradigm both for the other modules in the LDL receptor and for the homologous domains of several other proteins. Calcium ions had only minor effects on the CD spectrum and no effect on the 1H NMR spectrum of the repeat, suggesting that they induce no significant conformational change.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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Created: Tue, 08 Jan 2013, 14:45:55 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences