6BCS
LilrB2 D1D2 domains complexed with benzamidine
Summary for 6BCS
| Entry DOI | 10.2210/pdb6bcs/pdb |
| Descriptor | Leukocyte immunoglobulin-like receptor subfamily B member 2, BENZAMIDINE, CHLORIDE ION, ... (5 entities in total) |
| Functional Keywords | receptor, ig like domains, immune system |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 22773.67 |
| Authors | Cao, Q.,Sawaya, M.R.,Eisenberg, D.S. (deposition date: 2017-10-20, release date: 2018-09-05, Last modification date: 2024-10-23) |
| Primary citation | Cao, Q.,Shin, W.S.,Chan, H.,Vuong, C.K.,Dubois, B.,Li, B.,Murray, K.A.,Sawaya, M.R.,Feigon, J.,Black, D.L.,Eisenberg, D.S.,Jiang, L. Inhibiting amyloid-beta cytotoxicity through its interaction with the cell surface receptor LilrB2 by structure-based design. Nat Chem, 10:1213-1221, 2018 Cited by PubMed Abstract: Inhibiting the interaction between amyloid-β (Aβ) and a neuronal cell surface receptor, LilrB2, has been suggested as a potential route for treating Alzheimer's disease. Supporting this approach, Alzheimer's-like symptoms are reduced in mouse models following genetic depletion of the LilrB2 homologue. In its pathogenic, oligomeric state, Aβ binds to LilrB2, triggering a pathway to synaptic loss. Here we identify the LilrB2 binding moieties of Aβ (KLVFFA) and identify its binding site on LilrB2 from a crystal structure of LilrB2 immunoglobulin domains D1D2 complexed to small molecules that mimic phenylalanine residues. In this structure, we observed two pockets that can accommodate the phenylalanine side chains of KLVFFA. These pockets were confirmed to be KLVFFA binding sites by mutagenesis. Rosetta docking revealed a plausible geometry for the Aβ-LilrB2 complex and assisted with the structure-guided selection of small molecule inhibitors. These molecules inhibit Aβ-LilrB2 interactions in vitro and on the cell surface and reduce Aβ cytotoxicity, which suggests these inhibitors are potential therapeutic leads against Alzheimer's disease. PubMed: 30297750DOI: 10.1038/s41557-018-0147-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
Download full validation report
