HSPA8

HSPA8 is a protein that in humans is encoded by the HSPA8 gene. This gene is a member of the heat shock protein 70 family (HSP70), which are known for their role in cellular stress response and protein folding. HSPA8, also known as heat shock cognate 71 kDa protein (Hsc70), is constitutively expressed in most cells and is involved in various cellular processes including protein folding, repair, and assembly, as well as the regulation of apoptosis and immune responses.

Function

HSPA8 is a highly conserved molecular chaperone that assists in the folding of nascent polypeptide chains and the refolding of denatured proteins, preventing their aggregation. It is involved in the transport of proteins across membranes and in the targeting of proteins for lysosomal degradation. HSPA8 interacts with a wide range of co-chaperones and client proteins, facilitating their correct folding and functional state. It plays a critical role in maintaining cellular proteostasis and responding to cellular stress conditions.

Structure

The structure of HSPA8 is characterized by a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). The NBD binds and hydrolyzes ATP, which is essential for the chaperone activity of HSPA8. The SBD is responsible for the interaction with polypeptide substrates. The C-terminal region of HSPA8 contains a conserved EEVD motif that is involved in the interaction with co-chaperones containing tetratricopeptide repeat (TPR) domains.

Clinical Significance

Alterations in the expression and function of HSPA8 have been associated with various diseases, including cancer, neurodegenerative diseases (such as Alzheimer's disease and Parkinson's disease), and infectious diseases. HSPA8 is considered a potential therapeutic target, and modulating its expression or function may offer new approaches for the treatment of these conditions.

Research

Research on HSPA8 continues to uncover its diverse roles in cellular physiology and its potential as a therapeutic target. Studies have explored its involvement in the immune response, its role in the pathogenesis of diseases, and its potential as a biomarker for certain conditions.