4KJY

Complex of high-affinity SIRP alpha variant FD6 with CD47

4KJY の概要

• エントリーDOI: 10.2210/pdb4kjy/pdb
• 分子名称: Leukocyte surface antigen CD47, High-affinity SIRPa variant FD6, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: immunoglobulin fold, immune regulation, n-linked glycosylation, plasma membrane, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 59594.35

構造登録者

Ring, A.M.,Ozkan, E.,Ho, C.C.M.,Garcia, K.C. (登録日: 2013-05-04, 公開日: 2013-06-12, 最終更新日: 2024-11-06)

主引用文献

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

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: 23722425
DOI: 10.1126/science.1238856

実験手法

X-RAY DIFFRACTION (1.93 Å)