Summary for 5MJ3
| Entry DOI | 10.2210/pdb5mj3/pdb |
| Descriptor | Interleukin-12 subunit beta, Interleukin-23 subunit alpha, ALPHABODY MA12, ... (8 entities in total) |
| Functional Keywords | designed antiparallel triple-helix coiled-coil, alphabody, immunoglobulin domain, 4-helical bundle cytokine, antagonist, n-linked glycosylation, alkylation, immune system |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 67949.25 |
| Authors | Desmet, J.,Verstraete, K.,Bloch, Y.,Lorent, E.,Wen, Y.,Devreese, B.,Vandenbroucke, K.,Loverix, S.,Hettmann, T.,Deroo, S.,Somers, K.,Hendrikx, P.,Lasters, I.,Savvides, S.N. (deposition date: 2016-11-29, release date: 2017-01-11, Last modification date: 2024-01-17) |
| Primary citation | Desmet, J.,Verstraete, K.,Bloch, Y.,Lorent, E.,Wen, Y.,Devreese, B.,Vandenbroucke, K.,Loverix, S.,Hettmann, T.,Deroo, S.,Somers, K.,Henderikx, P.,Lasters, I.,Savvides, S.N. Structural Basis Of Il-23 Antagonism By An Alphabody Protein Scaffold. Nat Commun, 5:5237-, 2014 Cited by PubMed Abstract: Protein scaffolds can provide a promising alternative to antibodies for various biomedical and biotechnological applications, including therapeutics. Here we describe the design and development of the Alphabody, a protein scaffold featuring a single-chain antiparallel triple-helix coiled-coil fold. We report affinity-matured Alphabodies with favourable physicochemical properties that can specifically neutralize human interleukin (IL)-23, a pivotal therapeutic target in autoimmune inflammatory diseases such as psoriasis and multiple sclerosis. The crystal structure of human IL-23 in complex with an affinity-matured Alphabody reveals how the variable interhelical groove of the scaffold uniquely targets a large epitope on the p19 subunit of IL-23 to harness fully the hydrophobic and hydrogen-bonding potential of tryptophan and tyrosine residues contributed by p19 and the Alphabody, respectively. Thus, Alphabodies are suitable for targeting protein-protein interfaces of therapeutic importance and can be tailored to interrogate desired design and binding-mode principles via efficient selection and affinity-maturation strategies. PubMed: 25354530DOI: 10.1038/NCOMMS6237 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.74 Å) |
Structure validation
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