7DC8

Crystal structure of Switch Ab Fab and hIL6R in complex with ATP

Summary for 7DC8

• Entry DOI: 10.2210/pdb7dc8/pdb
• Descriptor: Switch Ab Fab light chain, Switch Ab Fab heavy chain, Interleukin-6 receptor subunit alpha, ... (6 entities in total)
• Functional Keywords: antibody, complex, fab, immune system, cytokine
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 147116.62

Authors

Kadono, S.,Fukami, T.A.,Kawauchi, H.,Torizawa, T.,Mimoto, F. (deposition date: 2020-10-23, release date: 2021-01-13, Last modification date: 2024-10-30)

Primary citation

Mimoto, F.,Tatsumi, K.,Shimizu, S.,Kadono, S.,Haraya, K.,Nagayasu, M.,Suzuki, Y.,Fujii, E.,Kamimura, M.,Hayasaka, A.,Kawauchi, H.,Ohara, K.,Matsushita, M.,Baba, T.,Susumu, H.,Sakashita, T.,Muraoka, T.,Aso, K.,Katada, H.,Tanaka, E.,Nakagawa, K.,Hasegawa, M.,Ayabe, M.,Yamamoto, T.,Tanba, S.,Ishiguro, T.,Kamikawa, T.,Nambu, T.,Kibayashi, T.,Azuma, Y.,Tomii, Y.,Kato, A.,Ozeki, K.,Murao, N.,Endo, M.,Kikuta, J.,Kamata-Sakurai, M.,Ishii, M.,Hattori, K.,Igawa, T.
Exploitation of Elevated Extracellular ATP to Specifically Direct Antibody to Tumor Microenvironment.
Cell Rep, 33:108542-108542, 2020

PubMed Abstract: The extracellular adenosine triphosphate (ATP) concentration is highly elevated in the tumor microenvironment (TME) and remains tightly regulated in normal tissues. Using phage display technology, we establish a method to identify an antibody that can bind to an antigen only in the presence of ATP. Crystallography analysis reveals that ATP bound in between the antibody-antigen interface serves as a switch for antigen binding. In a transgenic mouse model overexpressing the antigen systemically, the ATP switch antibody binds to the antigen in tumors with minimal binding in normal tissues and plasma and inhibits tumor growth. Thus, we demonstrate that elevated extracellular ATP concentration can be exploited to specifically target the TME, giving therapeutic antibodies the ability to overcome on-target off-tumor toxicity.

PubMed: 33357423
DOI: 10.1016/j.celrep.2020.108542

Experimental method

X-RAY DIFFRACTION (2.757 Å)