4CNM
Crystal structure of human 5T4 (Wnt-activated inhibitory factor 1, Trophoblast glycoprotein)
Summary for 4CNM
| Entry DOI | 10.2210/pdb4cnm/pdb |
| Related | 4CNC |
| Descriptor | TROPHOBLAST GLYCOPROTEIN, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | cell adhesion, waif1, tpbg, trovax, mva-5t4, cancer, signaling, leucine-rich repeats, wnt/beta-catenin signaling pathway |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Membrane; Single-pass type I membrane protein (Potential): Q13641 |
| Total number of polymer chains | 1 |
| Total formula weight | 34932.35 |
| Authors | Zhao, Y.,Malinauskas, T.,Harlos, K.,Jones, E.Y. (deposition date: 2014-01-23, release date: 2014-02-26, Last modification date: 2023-12-20) |
| Primary citation | Zhao, Y.,Malinauskas, T.,Harlos, K.,Jones, E.Y. Structural Insights Into the Inhibition of Wnt Signaling by Cancer Antigen 5T4/Wnt-Activated Inhibitory Factor 1. Structure, 22:612-, 2014 Cited by PubMed Abstract: The tumor antigen 5T4/WAIF1 (Wnt-activated inhibitory factor 1; also known as Trophoblast glycoprotein TPBG) is a cell surface protein targeted in multiple cancer immunotherapy clinical trials. Recently, it has been shown that 5T4/WAIF1 inhibits Wnt/β-catenin signaling, a signaling system central to many developmental and pathological processes. Wnt/β-catenin signaling is controlled by multiple inhibitors and activators. Here, we report crystal structures for the extracellular domain of 5T4/WAIF1 at 1.8 Å resolution. They reveal a highly glycosylated, rigid core, comprising eight leucine-rich repeats (LRRs), which serves as a platform to present evolutionarily conserved surface residues in the N-terminal LRR1. Structural and cell-based analyses, coupled with previously reported in vivo data, suggest that Tyr325 plus the LRR1 surface centered on a second exposed aromatic residue, Phe97, are essential for inhibition of Wnt/β-catenin signaling. These results provide a structural basis for the development of 5T4/WAIF1-targeted therapies that preserve or block 5T4/WAIF1-mediated inhibition of Wnt/β-catenin signaling. PubMed: 24582434DOI: 10.1016/J.STR.2014.01.009 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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