7WG3

Structural basis of interleukin-17B receptor in complex with a neutralizing antibody D9 for guiding humanization and affinity maturation for cancer therapy

Summary for 7WG3

• Entry DOI: 10.2210/pdb7wg3/pdb
• Descriptor: Light chain of D9 Fab, Heavy chain of D9 Fab, IL17RB protein, ... (7 entities in total)
• Functional Keywords: il-17b, il17rb, antibody, complex, interleukin-17 b receptor, pancreatic cancer, cancer target therapy, antibody engineering, immune system
• Biological source: Mus musculus; More
• Total number of polymer chains: 12
• Total formula weight: 305745.57

Authors

Lee, W.H.,Chen, X.R.,Liu, I.J.,Lee, J.H.,Hu, C.M.,Wu, H.C.,Wang, S.K.,Lee, W.H.,Ma, C. (deposition date: 2021-12-28, release date: 2022-11-09, Last modification date: 2024-11-13)

Primary citation

Lee, W.H.,Chen, X.,Liu, I.J.,Lee, J.H.,Hu, C.M.,Wu, H.C.,Wang, S.K.,Lee, W.H.,Ma, C.
Structural basis of interleukin-17B receptor in complex with a neutralizing antibody for guiding humanization and affinity maturation.
Cell Rep, 41:111555-111555, 2022

PubMed Abstract: Upregulation of interleukin-17 receptor B (IL-17RB) is known to be oncogenic, while other IL-17 receptors and ligands are generally involved in pro-inflammatory pathways. We identify a mouse neutralizing monoclonal antibody (mAb) D9, which blocks the IL-17RB/IL-17B pathway and inhibits pancreatic tumorigenesis in an orthotopic mouse model. The X-ray crystal structure of the IL-17RB ectodomain in complex with its neutralizing antibody D9 shows that D9 binds to a predicted ligand binding interface and engages with the A'-A loop of IL-17RB fibronectin III domain 1 in a unique conformational state. This structure also provides important paratope information to guide the design of antibody humanization and affinity maturation of D9, resulting in a humanized 1B12 antibody with marginal affinity loss and effective neutralization of IL-17B/IL-17RB signaling to impede tumorigenesis in a mouse xenograft model.

PubMed: 36288706
DOI: 10.1016/j.celrep.2022.111555

Experimental method

X-RAY DIFFRACTION (2.19 Å)