6FAX
Complex of Human CD40 Ectodomain with Lob 7.4 Fab
Summary for 6FAX
| Entry DOI | 10.2210/pdb6fax/pdb |
| Descriptor | Lob 7.4 light chain, Lob 7.4 heavy chain, Tumor necrosis factor receptor superfamily member 5, ... (4 entities in total) |
| Functional Keywords | cd40, engineered fab, agonist, mab, immune system |
| Biological source | Homo sapiens More |
| Cellular location | Isoform I: Cell membrane; Single-pass type I membrane protein. Isoform II: Secreted: P25942 |
| Total number of polymer chains | 3 |
| Total formula weight | 68515.46 |
| Authors | Orr, C.M.,Tews, I.,Pearson, A.R. (deposition date: 2017-12-18, release date: 2018-02-07, Last modification date: 2024-11-06) |
| Primary citation | Yu, X.,Chan, H.T.C.,Orr, C.M.,Dadas, O.,Booth, S.G.,Dahal, L.N.,Penfold, C.A.,O'Brien, L.,Mockridge, C.I.,French, R.R.,Duriez, P.,Douglas, L.R.,Pearson, A.R.,Cragg, M.S.,Tews, I.,Glennie, M.J.,White, A.L. Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies. Cancer Cell, 33:664-675.e4, 2018 Cited by PubMed Abstract: Anti-CD40 monoclonal antibodies (mAbs) that promote or inhibit receptor function hold promise as therapeutics for cancer and autoimmunity. Rules governing their diverse range of functions, however, are lacking. Here we determined characteristics of nine hCD40 mAbs engaging epitopes throughout the CD40 extracellular region expressed as varying isotypes. All mAb formats were strong agonists when hyper-crosslinked; however, only those binding the membrane-distal cysteine-rich domain 1 (CRD1) retained agonistic activity with physiological Fc gamma receptor crosslinking or as human immunoglobulin G2 isotype; agonistic activity decreased as epitopes drew closer to the membrane. In addition, all CRD2-4 binding mAbs blocked CD40 ligand interaction and were potent antagonists. Thus, the membrane distal CRD1 provides a region of choice for selecting CD40 agonists while CRD2-4 provides antagonistic epitopes. PubMed: 29576376DOI: 10.1016/j.ccell.2018.02.009 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.99 Å) |
Structure validation
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