Real-Time Analysis of Binding Events between Different Aβ_1-42 Species and Human Lilrb2 by Dual Polarization...

Abnormal accumulation of 42-residue amyloid-β (Aβ_1-42) 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 Aβ_1-42 species such as monomeric Aβ_1-42, low molecular weight Aβ_1-42 oligomer (LMW Aβ_1-42), and high molecular weight Aβ_1-42 oligomer (HMW Aβ_1-42) 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 (k_a) of ED1D2L receptor with monomeric Aβ_1-42, LMW Aβ_1-42, and HMW Aβ_1-42 is individually determined to be 2.85 × 10⁴, 4.52 × 10⁴, and 1.34 × 10⁵ M^-1·s^-1, and meanwhile, the dissociation rate (k_d) 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 k_a and k_d values, we discovery that the HMW Aβ_1-42 exhibits the fastest rate for ED1D2L receptor in the association phrase, and HMW Aβ_1-42 likewise shows the highest affinity with ED1D2L receptor during the dissociation period in contrast to LMW Aβ_1-42 and monomeric Aβ_1-42. 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 Aβ_1-42. Strikingly, this work offers a new exciting clue to explore the dynamic properties associated with interactions of various Aβ_1-42 species with other targets and hopefully contributes to drug discovery and screen in the future.