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Structure of the minimal interface between ApoE and LRP

Miklos Guttman1, J Helena Prieto, Tracy M Handel

  • 1Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0378, USA.

Journal of Molecular Biology
|March 23, 2010
PubMed

Insights

Researchers studied the interaction between Apolipoprotein E (ApoE) and low-density lipoprotein receptor (LDLR) family proteins. They found that binding ApoE to a specific LDLR repeat (CR17) caused significant dynamic changes, revealing insights into cholesterol homeostasis mechanisms.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Interactions

Background:

  • Complement-type repeats (CRs) in the low-density lipoprotein receptor (LDLR) family mediate ligand interactions.
  • Apolipoprotein E (ApoE) is crucial for cholesterol homeostasis and interacts with LDLR-related protein 1 (LRP) via CRs.
  • The ApoE receptor-binding segment (residues 130-149) shows weak affinity for isolated CRs.

Purpose of the Study:

  • To elucidate the structure of a complex formed by a high-affinity LRP CR (CR17) and the ApoE receptor-binding segment.
  • To investigate the structural and dynamic changes upon complex formation.

Main Methods:

  • Protein engineering: Fusing the ApoE receptor-binding segment to CR17.
  • Structural elucidation of the complex.
  • Nuclear Magnetic Resonance (NMR) perturbation experiments to study dynamics.

Main Results:

  • The interface revealed a known motif with novel features.
  • Minimal structural changes were observed in CR17 upon binding.
  • Significant alterations in the intrinsic dynamics of CR17 were detected after binding ApoE.
  • NMR data suggest this interface resembles other LDLR-ligand interactions.

Conclusions:

  • The study provides structural and dynamic insights into the ApoE-LRP interaction.
  • Binding of ApoE to CR17 induces significant dynamic changes, rather than major structural rearrangements.
  • The findings may generalize to other ligand interactions within the LDLR superfamily, impacting cholesterol transport understanding.

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