Recombinant Human TRRAP protein

TRRAP (Transformation/Transcription Domain-Associated Protein) is a large, evolutionarily conserved scaffold protein belonging to the phosphatidylinositol 3-kinase-related kinase (PIKK) family. Unlike other PIKK members, TRRAP lacks intrinsic kinase activity due to critical amino acid substitutions in its catalytic domain. Discovered in the late 1990s, it gained attention for its role in transcriptional regulation and DNA damage response. TRRAP serves as a core component of multiple chromatin-modifying complexes, including histone acetyltransferase (HAT) complexes like Tip60 and GCN5. which regulate gene expression by modifying chromatin structure.

Its biological significance spans DNA repair, cell cycle control, and embryonic development. TRRAP interacts with oncogenic transcription factors (e.g., MYC, E2F) and tumor suppressors (e.g., p53), positioning it at the crossroads of cancer biology. Studies show TRRAP depletion leads to genomic instability and impaired cell proliferation, underscoring its essential role in maintaining cellular homeostasis.

Recombinant TRRAP proteins are engineered to study its molecular interactions and structural features. However, producing full-length TRRAP (over 3.800 amino acids) remains challenging due to its size and complex domain architecture, featuring multiple HEAT repeats. Most studies use truncated variants or co-expression systems to overcome solubility issues. These recombinant tools have enabled mapping of binding interfaces with MYC, p53. and HAT complex subunits, advancing drug discovery efforts targeting TRRAP-dependent pathways in cancers and neurodegenerative diseases. Recent cryo-EM studies using recombinant TRRAP fragments have also shed light on its role in organizing multi-protein chromatin complexes.