4cnm is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
5T4/WAIF1, also called Trophoblast glycoprotein ( TPBG) is a protein expressed on the surface of embryonic and tumoral cells: it is rarely found in adult tissues. It has first been identified in human placental tissues.
Structure [1]
5T4’s molecular weight is MW=72 kDa, and it contains 420 amino acid residues. Its particularity is that it is a heavily glycosylated protein.The are the amino acid 81, 124, 166, 192, 243, 256, 275. 5T4 is a transmembrane protein that crosses the membrane only once.
This protein can be divided in 5 main parts. First there is a secretion signal region, then a serine- rich part, leucine rich repeats (LRRs), a transmembrane region and finally a short cytoplasmic tail.
The structure showed corresponds only to the extra cellular part of the protein, that is composed of the peptide signal, the serine rich part and 8 LRRs. The peptide signal is a signal sequence whose function is to address the nascent protein to wherever it is supposed to be: here this signal peptides direct the protein to the membrane. LRRs are a structural motif rich in leucine. In this protein LRRs motifs are adjacent. The unit that is repeated in this structural motif is a β strand, linked to an α helix by a turn. The β strand is inside the motif because it is composed of hydrophobic amino acids (leucine) contrarily to an α helix. β sheets are arranged in ladder in space. The 8 LRRs form the compact core of the extra cellular domain and they are divided in 3 main classes, each of them having a specific sequence motif of amino acid. The Nter and Cter tails contain 2 disulfide bonds that may stabilize the LRR core.
The transmembrane region is an α helix. On the cytoplasmic part there is a PDZ motif that can interact with an other TIP-2/GIPC, a protein that associates with vesicles located near the cell membrane.
There are 2 main amino acids that are essential for the protein functioning: and . They are crucial in the inhibition mechanism of Wnt/ βcatering signaling pathway.
There are many molecules that can bind to the protein:
Function
5T4 inhibits Wnt/ βcatenin signaling which is a significant signaling system in many developments and pathological processes. This protein is involved in many biological mechanisms of cell migration and implantation. During embryogenesis 5T4 is linked to processes like formation of placenta or adhesion of the embryo on the uterus walls. In the case of cancer the overexpression of 5T4 in cells can explain the acquirement of migratory phenotype.
Disease [2]
This protein developing on the surface of tumoral cells is studied in the cancer research. It can be use for instance in immunotherapy, a technique that uses the immune system to attacks the tumor cells. The tumor antigen is a substance of the cell leading to immune answer. The antibodies are designed in the lab to recognise specifically the antigens. They are added later, and interact with the antigens. The immune system detects this complex as a stranger body and destroys the cell that carries it. Tumor associated antigens ( TAA) are used for the diagnostic and immunotherapy. 5T4 has criterias of a TAA and thus may be an efficient antigen to destroy cancer cells.
