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Effective inhibition of C3a-mediated pro-inflammatory response by a human C3a-specific protein binder |
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| Authors: | Yoo-Kyoung Sohn Sumin Son Yoonjoo Choi Da-Eun Hwang Hyo-Deok Seo Joong-jae Lee Hak-Sung Kim |
| Institution: | 1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea;2. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea
Department of Statistics, Seoul National University, Seoul, Korea;3. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea Yuhan Research Institute, Yuhan Corporation, Yongin, Korea;4. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea Research Group of Natural Materials and Metabolism, Korea Food Research Institute (KFRI), Jeollabuk-do, Korea;5. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea Department of Biochemistry, Kangwon National University, Chuncheon, Korea |
| Abstract: | Complement component 3a (C3a) plays a crucial role in the immune response and host defense, but it is also involved in pro-inflammatory responses, causing many inflammatory disorders. Blockade of C3a has been regarded as a potent therapeutic strategy for inflammatory diseases. Here, we present the development of a human C3a (hC3a)-specific protein binder, which effectively inhibits pro-inflammatory responses. The protein binder, which is composed of leucine-rich repeat modules, was selected against hC3a through phage display, and its binding affinity was matured up to 600 pM by further expanding the binding interface in a module-by-module manner. The developed protein binder was shown to have more than 10-fold higher specificity to hC3a compared with human C5a, exhibiting a remarkable suppression effect on pro-inflammatory response in monocyte, by blocking the interaction between hC3a and its receptor. The hC3a-specific protein binder is likely to have a therapeutic potential for C3a-mediated inflammatory diseases. |
| Keywords: | anaphylatoxin C3a inflammatory disease protein binder protein engineering repebody |