8X0T

Frizzled8 CRD in complex with pF8_AC3 Fab

Summary for 8X0T

• Entry DOI: 10.2210/pdb8x0t/pdb
• Descriptor: Frizzled-8, pF8_AC3 Heavy chain, pF8_AC3 Light chain, ... (4 entities in total)
• Functional Keywords: antigen-antibody complex, cell signaling, signaling protein/immune system, signaling protein-immune system complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 63252.86

Authors

Li, N.,Ge, Q. (deposition date: 2023-11-06, release date: 2023-11-22, Last modification date: 2024-11-20)

Primary citation

Li, N.,Ge, Q.,Guo, Q.,Tao, Y.
Identification and functional validation of FZD8-specific antibodies.
Int J Biol Macromol, 254:127846-, 2023

PubMed Abstract: The Wnt pathway is an evolutionarily conserved pathway involved in stem cell homeostasis and tissue regeneration. Aberrant signaling in the Wnt pathway is highly associated with cancer. Developing antibodies to block overactivation of Frizzled receptors (FZDs), the main receptors in the Wnt pathway, is one of the viable options for treating cancer. However, obtaining isoform-specific antibodies is often challenging due to the high degree of homology among the ten FZDs. In this study, by using a synthetic library, we identified an antibody named pF8_AC3 that preferentially binds to FZD8. Guided by the structure of the complex of pF8_AC3 and FZD8, a second-generation targeted library was further constructed, and finally, the FZD8-specific antibody sF8_AG6 was obtained. Cell-based assays showed that these antibodies could selectively block FZD8-mediated signaling activation. Taken together, these antibodies have the potential to be developed into therapeutic drugs in the future.

PubMed: 37926311
DOI: 10.1016/j.ijbiomac.2023.127846

Experimental method

X-RAY DIFFRACTION (2.5 Å)