Recombinant TEAD3 (R218-D435) YAP-binding domain, Transcriptional Enhanced Associate Domain 3, Transcriptional enhancer factor TEF-5

Our recombinant S_TEAD3(R218-D435) protein contains the C-terminal YAP-binding domain of the human transcription factor TEAD3. It has an additional N-terminal Serine, which remains from the TEV cleavage site.

Protein Construct: TEAD3(R218-D435)
Source: Human
Expression Host: Escherichia coli
Molecular weight [kDa]: 25.1
pI: 6.7
Extinction Coefficient [M^-1cm^-1]: 21890
Concentration: 10 mg/mL
Storage Buffer: 20 mM Tris pH 7.5, 150 mM NaCl, 5% Glycerol, 2 mM DTT
Tag: none

Amino acid sequence:

QC Data: Datasheet
Purity SDS: >95 %
Hydrodynamic Radius (nm): 2.78
Polydispersity Index (PDI): 0.13
T_m (°C): 63.3
T_on (°C): 56.9

Structure and function

TEAD3 is part of the TEAD transcription factor family that regulates important cellular functions like tissue homeostasis, cell growth and proliferation. TEAD3 drives gene expression via its highly conserved TEA DNA-binding domain, which folds into a three-helix bundle. The H3 helix incorporates the DNA recognition surface which features 3 serines essential for DNA binding activities. In addition TEAD3 has a C-terminal interaction domain, which enables binding to transcriptional cofactor Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), which is obligatory for TEAD3 to regulate transcription. The C-terminal domain adopts an immunoglobulin-like ß-sandwich fold while the YAP itself is mostly unstructured and only forms secondary structure elements upon binding to TEAD3. Both TEA domain and C-terminal domain are connected via a proline-rich region, which is necessary for interaction of the C-terminal domain with YAP/TAZ.

TEAD3 as an important drug target

TEAD3 is a transcription factor that functions downstream of the oncogenic co-activators YAP and TAZ, key effectors of the Hippo signaling pathway. The interaction with YAP/TAZ, enables TEAD3 to bind DNA and regulates the expression of genes involved in proliferation, differentiation, and apoptosis. Hippo signaling controls gene expression largely through suppressing YAP and TAZ. In several types of cancer, however, dysregulation of Hippo signaling causes YAP/TAZ accumulation and tumor progression, making inhibition of the interaction of TEAD3 with YAP a promising therapeutic strategy.
One interaction inhibition strategy involves a hydrophobic pocket in the C-terminal region which is under physiological conditions occupied by a palmitate molecule binding to a conserved cysteine. This pocket has been shown to be important for TEAD3 stability as well as the TEAD3-YAP interaction, leading to the development of several small molecule inhibitors targeting this site. Another TEAD3 inhibition strategy is targeting the transcription factor with Proteolysis-targeting chimeras (PROTACs), which recruit the protein to an E3 ligase, thereby inducing its ubiquitination and degradation by the proteasome.
TEAD3 is not only an important target in cancer research but has also become the focus of reproductive biology due to its association with maternal-fetal immune tolerance. In addition, studies in neuroscience have provided initial evidence for the involvement of TEAD3 in neural development and have linked it to neurodegenerative diseases such as Alzheimer's disease.