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NMR studies of the low-density lipoprotein receptor-binding peptide of apolipoprotein E bound to dodecylphosphocholine micelles

Published online by Cambridge University Press:  01 September 1999

DANIEL CLAYTON
Affiliation:
Department of Biochemistry, University of Queensland, Queensland 4072, Australia
IAN M. BRERETON
Affiliation:
Center for Magnetic Resonance, University of Queensland, Queensland 4072, Australia
PAULUS A. KROON
Affiliation:
Department of Biochemistry, University of Queensland, Queensland 4072, Australia
ROSS SMITH
Affiliation:
Department of Biochemistry, University of Queensland, Queensland 4072, Australia
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Abstract

Circular dichroism and NMR spectroscopy have been used to determine the structure of the low-density lipoprotein (LDL) receptor-binding peptide, comprising residues 130–152, of the human apolipoprotein E. This peptide has little persistent three-dimensional structure in solution, but when bound to micelles of dodecylphosphocholine (DPC) it adopts a predominantly α-helical structure. The three-dimensional structure of the DPC-bound peptide has been determined by using 1H-NMR spectroscopy: the structure derived from NOE-based distance constraints and restrained molecular dynamics is largely helical. The derived φ and ψ angle order parameters show that the helical structure is well defined but with some flexibility that causes the structures not to be superimposable over the full peptide length. Deuterium exchange experiments suggest that many peptide amide groups are readily accessible to the solvent, but those associated with hydrophobic residues exchange more slowly, and this helix is thus likely to be positioned on the surface of the DPC micelles. In this conformation the peptide has one hydrophobic face and two that are rich in basic amino acid side chains. The solvent-exposed face of the peptide contains residues previously shown to be involved in binding to the LDL receptor.

Type
Research Article
Copyright
© 1999 The Protein Society

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