Structure of the minimal interface between ApoE and LRP.

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.