Journal
ANALYTICAL CHEMISTRY
Volume 89, Issue 4, Pages 2606-2612Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.6b04950
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Funding
- National Natural Science Foundation of China [21435005, 21627808]
- Key Research Program of Frontier Sciences, CAS [QYZDY-SSW-SLH019]
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Abnormal accumulation of 42-residue amyloid-beta (A beta(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 A beta(1-42) species such as monomeric A beta(1-42), low molecular weight A beta(1-42) oligomer (LMW A beta(1-42)), and high molecular weight A beta(1-42) oligomer (HMW A beta(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 A beta(1-42), LMW A beta(1)-(42), and HMWA beta(1-42) is individually determined to be 2.85 x 10(4), 4.52 X 10(4), and 1.34 X 10(5) M-1.s-(1), and meanwhile, the dissociation rate (k(d)) corresponds to 1.79 x 10(-2), 2.09 X 10(-2), and 5.34 X 10(-4) s(-1), respectively. By analysis of the kinetic parameters of ka and kd values, we discovery that the HMW A beta(1-42) exhibits the fastest rate for ED1D2L receptor in the association phrase, and HMW A beta(1)-(42) likewise shows the highest affinity with ED1D2L receptor during the dissociation period in contrast to LMW A beta(1-42) and monomeric A beta(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 A beta(1-42). Strikingly, this work offers a new exciting clue to explore the dynamic properties associated with interactions of various A beta(1-42) species with other targets and hopefully contributes to drug discovery and screen in the future.
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