Recombinant Human PKD1 protein

The PKD1 (Polycystin-1) recombinant protein is derived from the PKD1 gene, which encodes a large transmembrane glycoprotein critical for normal renal tubule development and function. Mutations in PKD1 account for approximately 85% of autosomal dominant polycystic kidney disease (ADPKD) cases, a genetic disorder characterized by progressive cyst formation in the kidneys, leading to organ enlargement and eventual renal failure. Polycystin-1. the protein product of PKD1. is thought to regulate cell proliferation, apoptosis, and fluid secretion through interactions with signaling pathways like Wnt, mTOR, and G-protein-coupled receptors. However, its full mechanistic role remains incompletely understood due to its structural complexity and large size (>4.300 amino acids).

Recombinant PKD1 proteins are engineered using heterologous expression systems (e.g., mammalian cells or insect cells) to produce functional domains or truncated variants, as full-length protein expression remains technically challenging. These recombinant tools enable researchers to study polycystin-1's extracellular ligand interactions, intracellular signaling cascades, and pathogenic mutations in vitro. Common applications include investigating cystogenesis mechanisms, validating drug candidates targeting ADPKD, and developing diagnostic assays. Notably, recombinant proteins containing the PKD1 N-terminal extracellular region have been used to map binding partners involved in cell-matrix adhesion, while cytoplasmic C-terminal fragments help elucidate pathways regulating renal tubular morphogenesis.

Despite advances, challenges persist in maintaining the native conformation and post-translational modifications of recombinant PKD1. which are crucial for its biological activity. Ongoing efforts focus on optimizing expression systems and cryo-EM structural studies to advance therapeutic discovery for polycystic kidney diseases.