Human Heat shock protein family A member 4 like (HSPA4L) is expressed ubiquitously and predominantly in the testis. It is required for normal spermatogenesis and plays a role in osmotolerance. HSPA4L belongs to the 105/110kDa heat shock protein (HSP105/110) subfamily of the HSP70-like family [, ]. HSP105/110s are believed to function generally as co-chaperones of HSP70 chaperones, acting as nucleotide exchange factors (NEFs), to remove ADP from their HSP70 chaperone partners during the ATP hydrolysis cycle []. HSP70 chaperones assist in protein folding and assembly, and can direct incompetent "client"proteins towards degradation. Like HSP70 chaperones, HSP105/110s have an N-terminal nucleotide-binding domain (NBD) and a C-terminal substrate-binding domain (SBD). For HSP70 chaperones, the nucleotide sits in a deep cleft formed between the two lobes of the NBD. The two subdomains of each lobe change conformation between ATP-bound, ADP-bound, and nucleotide-free states []. ATP binding opens up the substrate-binding site; substrate-binding increases the rate of ATP hydrolysis. Hsp70 chaperone activity is also regulated by J-domain proteins [, , ].
