PFDN5 Human

Prefoldin Subunit 5 (PFDN5) is a protein encoded by the PFDN5 gene in humans. It is a member of the prefoldin alpha subunit family and is one of the six subunits that make up the prefoldin complex . Prefoldin is a molecular chaperone complex that plays a crucial role in the correct folding of newly synthesized polypeptides, thereby preventing protein misfolding and aggregation .

The prefoldin complex is a heterohexameric co-chaperone consisting of six subunits: two alpha-like subunits (PFDN3 and PFDN5) and four beta-like subunits (PFDN1, PFDN2, PFDN4, and PFDN6) . The complex has a unique jellyfish-like structure with coiled-coil tentacles that participate in substrate binding . This structure allows prefoldin to bind and stabilize nascent polypeptides, facilitating their proper folding in an environment where there are many competing pathways for nonnative proteins .

PFDN5, specifically, binds to cytosolic chaperonin (c-CPN) and transfers target proteins to it . It also represses the transcriptional activity of the MYC oncogene, which is involved in cell cycle regulation, apoptosis, and cellular transformation .

Prefoldin plays a vital role in various cellular processes, including the assembly of cytoskeletal proteins such as actin and tubulin . These proteins are essential for cell division, motility, molecular transport, cytoskeletal stability, and biological signal transduction . The prefoldin complex, by assisting in the correct folding of these proteins, ensures the proper functioning of these critical cellular processes .

Abnormal expression of prefoldin subunits, including PFDN5, has been linked to various diseases, particularly neurodegenerative disorders and cancers . For instance, prefoldin is implicated in the pathogenesis of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease . In cancer, PFDN5 has been shown to inhibit the activity of the c-Myc oncogene, thereby regulating tumor growth .

Research on prefoldin and its subunits, including PFDN5, has expanded into emerging fields such as nanoparticles and biomaterials . Understanding the complex functions of prefoldin and its subunits can provide insights into the mechanisms of protein misfolding and the pathogenesis of diseases caused by misfolded protein aggregation .

In a murine model, genetic disruption of the Pfdn5 gene has been shown to cause a syndrome characterized by photoreceptor degeneration, central nervous system abnormalities, and male infertility . This suggests that PFDN5 is essential for normal sensory and neuronal development .