4KJY
Complex of high-affinity SIRP alpha variant FD6 with CD47
Summary for 4KJY
| Entry DOI | 10.2210/pdb4kjy/pdb |
| Descriptor | Leukocyte surface antigen CD47, High-affinity SIRPa variant FD6, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | immunoglobulin fold, immune regulation, n-linked glycosylation, plasma membrane, immune system |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 59594.35 |
| Authors | Ring, A.M.,Ozkan, E.,Ho, C.C.M.,Garcia, K.C. (deposition date: 2013-05-04, release date: 2013-06-12, Last modification date: 2024-11-06) |
| Primary citation | Weiskopf, K.,Ring, A.M.,Ho, C.C.,Volkmer, J.P.,Levin, A.M.,Volkmer, A.K.,Ozkan, E.,Fernhoff, N.B.,van de Rijn, M.,Weissman, I.L.,Garcia, K.C. Engineered SIRP alpha variants as immunotherapeutic adjuvants to anticancer antibodies. Science, 341:88-91, 2013 Cited by PubMed Abstract: CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. Here, we modified the binding domain of human SIRPα, the receptor for CD47, for use as a CD47 antagonist. We engineered high-affinity SIRPα variants with about a 50,000-fold increased affinity for human CD47 relative to wild-type SIRPα. As high-affinity SIRPα monomers, they potently antagonized CD47 on cancer cells but did not induce macrophage phagocytosis on their own. Instead, they exhibited remarkable synergy with all tumor-specific monoclonal antibodies tested by increasing phagocytosis in vitro and enhancing antitumor responses in vivo. This "one-two punch" directs immune responses against tumor cells while lowering the threshold for macrophage activation, thereby providing a universal method for augmenting the efficacy of therapeutic anticancer antibodies. PubMed: 23722425DOI: 10.1126/science.1238856 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.93 Å) |
Structure validation
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