8OG0
Crystal structure of MJF14-6-4-2 Fab fragment in complex with epitope peptide
Summary for 8OG0
| Entry DOI | 10.2210/pdb8og0/pdb |
| Descriptor | Fab fragment light chain, Fab fragment heavy chain, Alpha-synuclein, ... (4 entities in total) |
| Functional Keywords | alpha synuclein, fab fragment, mjf14-6-4-2, epitope, immune system |
| Biological source | Oryctolagus cuniculus More |
| Total number of polymer chains | 3 |
| Total formula weight | 46864.98 |
| Authors | Tars, K.,Lieknina, I. (deposition date: 2023-03-17, release date: 2024-03-27, Last modification date: 2024-11-06) |
| Primary citation | Lieknina, I.,Reimer, L.,Pantelejevs, T.,Lends, A.,Jaudzems, K.,El-Turabi, A.,Gram, H.,Hammi, A.,Jensen, P.H.,Tars, K. Structural basis of epitope recognition by anti-alpha-synuclein antibodies MJFR14-6-4-2. NPJ Parkinsons Dis, 10:206-206, 2024 Cited by PubMed Abstract: Alpha-synuclein (α-syn) inclusions in the brain are hallmarks of so-called Lewy body diseases. Lewy bodies contain mainly aggregated α-syn together with some other proteins. Monomeric α-syn lacks a well-defined three-dimensional structure, but it can aggregate into oligomeric and fibrillar amyloid species, which can be detected using specific antibodies. Here we investigate the aggregate specificity of monoclonal MJFR14-6-4-2 antibodies. We conclude that partial masking of epitope in unstructured monomer in combination with a high local concentration of epitopes is the main reason for MJFR14-6-4-2 selectivity towards aggregates. Based on the structural insight, we produced mutant α-syn that when fibrillated is unable to bind MJFR14-6-4-2. Using these fibrils as a tool for seeding cellular α-syn aggregation, provides superior signal/noise ratio for detection of cellular α-syn aggregates by MJFR14-6-4-2. Our data provide a molecular level understanding of specific recognition of toxic amyloid oligomers, which is critical for the development of inhibitors against synucleinopathies. PubMed: 39463404DOI: 10.1038/s41531-024-00822-y PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.712 Å) |
Structure validation
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