title: Real-Time Analysis of Binding Events between Different Aβ1-42Species and Human Lilrb2 by Dual Polarization Interferometry.
abstract: 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 Aβ1-42species such as monomeric Aβ1-42, low molecular weight Aβ1-42oligomer (LMW Aβ1-42), and high molecular weight Aβ1-42oligomer (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 Aβ1-42is individually determined to be 2.85 × 104, 4.52 × 104, and 1.34 × 105M-1·s-1, and meanwhile, the dissociation rate (kd) corresponds to 1.79 × 10-2, 2.09 × 10-2, and 5.34 × 10-4s-1, respectively. By analysis of the kinetic parameters of kaand kdvalues, we discovery that the HMW Aβ1-42exhibits the fastest rate for ED1D2L receptor in the association phrase, and HMW Aβ1-42likewise shows the highest affinity with ED1D2L receptor during the dissociation period in contrast to LMW Aβ1-42and 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 Aβ1-42species with other targets and hopefully contributes to drug discovery and screen in the future.
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun, Jilin 130022, China.|Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun, Jilin 130022, China.|Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun, Jilin 130022, China.
authors.forename: Chuanxia
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun, Jilin 130022, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun, Jilin 130022, China.|Department of Chemistry, University of Science and Technology of China , Hefei, Anhui 230026, China.
authors.forename: Xiurong
authors.identifier: 0000-0002-1289-1248
authors.initials: X
authors.lastname: Yang
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D007368:Interferometry; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000378:metabolism*; D066329:Protein Aggregates; D011485:Protein Binding; D000072417:Protein Domains; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D066329:Protein Aggregates; D011971:Receptors, Immunologic; C075222:amyloid beta-protein (1-42)