Real-Time Analysis of Binding Events between Different Aβ 1-42 Species and Human Lilrb2 by Dual Polarization Interferometry

Anal Chem. 2017 Feb 21;89(4):2606-2612. doi: 10.1021/acs.analchem.6b04950. Epub 2017 Feb 3.


Abnormal accumulation of 42-residue amyloid-β (Aβ1-42) within the brain triggers the pathogenesis of Alzheimer's disease (AD). In this paper, we use a dual polarization interferometry (DPI) tool to evaluate the binding events of various Aβ1-42 species such as monomeric Aβ1-42, low molecular weight Aβ1-42 oligomer (LMW Aβ1-42), and high molecular weight Aβ1-42 oligomer (HMW Aβ1-42) with extracellular D1D2 domain of lilrb2 (ED1D2L) receptor that has been proved to be associated with AD. Based on the real-time binding information provided by DPI, the association rate (ka) of ED1D2L receptor with monomeric Aβ1-42, LMW Aβ1-42, and HMW Aβ1-42 is individually determined to be 2.85 × 104, 4.52 × 104, and 1.34 × 105 M-1·s-1, and meanwhile, the dissociation rate (kd) corresponds to 1.79 × 10-2, 2.09 × 10-2, and 5.34 × 10-4 s-1, respectively. By analysis of the kinetic parameters of ka and kd values, we discovery that the HMW Aβ1-42 exhibits the fastest rate for ED1D2L receptor in the association phrase, and HMW Aβ1-42 likewise shows the highest affinity with ED1D2L receptor during the dissociation period in contrast to LMW Aβ1-42 and monomeric Aβ1-42. Our findings significantly reveal the different binding behaviors among them from the perspective of kinetics aspect, by which we could indirectly elucidate the malicious impacts in the process of AD triggered by HMW Aβ1-42. Strikingly, this work offers a new exciting clue to explore the dynamic properties associated with interactions of various Aβ1-42 species with other targets and hopefully contributes to drug discovery and screen in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • HEK293 Cells
  • Humans
  • Immunoprecipitation
  • Interferometry*
  • Kinetics
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / metabolism*
  • Microscopy, Atomic Force
  • Peptide Fragments / metabolism*
  • Protein Aggregates
  • Protein Binding
  • Protein Domains
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / metabolism*


  • Amyloid beta-Peptides
  • LILRB2 protein, human
  • Membrane Glycoproteins
  • Peptide Fragments
  • Protein Aggregates
  • Receptors, Immunologic
  • amyloid beta-protein (1-42)