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PDBsum entry 4cnm
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Cell adhesion
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PDB id
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4cnm
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PDB id:
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| Name: |
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Cell adhesion
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Title:
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Crystal structure of human 5t4 (wnt-activated inhibitory factor 1, trophoblast glycoprotein)
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Structure:
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Trophoblast glycoprotein. Chain: a. Fragment: extracellular domain, residues 60-345. Synonym: 5t4 oncofetal antigen, wnt-activated inhibitory factor, 5t4 oncofetal trophoblast glycoprotein, 5t4 oncotrophoblast glycoprotein, m6p1. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293s gnti-. Expression_system_atcc_number: crl-3022.
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Resolution:
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1.75Å
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R-factor:
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0.184
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R-free:
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0.222
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Authors:
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Y.Zhao,T.Malinauskas,K.Harlos,E.Y.Jones
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Key ref:
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Y.Zhao
et al.
(2014).
Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1.
Structure,
22,
612-620.
PubMed id:
DOI:
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Date:
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23-Jan-14
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Release date:
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26-Feb-14
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PROCHECK
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Headers
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References
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Q13641
(TPBG_HUMAN) -
Trophoblast glycoprotein from Homo sapiens
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Seq:
Struc:
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420 a.a.
283 a.a.*
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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*
PDB and UniProt seqs differ
at 3 residue positions (black
crosses)
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DOI no:
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Structure
22:612-620
(2014)
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PubMed id:
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Structural insights into the inhibition of Wnt signaling by cancer antigen 5T4/Wnt-activated inhibitory factor 1.
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Y.Zhao,
T.Malinauskas,
K.Harlos,
E.Y.Jones.
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ABSTRACT
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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.
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