4.1.2. Hsp90

Hsp90 is a homodimer, and each of its monomers consists of a highly conserved amino-terminal domain (NTD) of ~25 kDa, a middle domain of ~40 kDa, and a C-terminal dimerization domain of ~12 kDa [70,71]. Hsp90 is also an ATP-dependent chaperone present in almost all the compartments of a eukaryotic cell. Hsp90 regulates the stability and maturation of >300 proteins that are key players in many biological processes, such as immune response, telomere maintenance, cancer development, steroid signaling, and vesicular transport [72]. To recognize its enormous number of client proteins, Hsp90 interacts with more than 20 co-chaperones. Hop, also known as p60, and STI1 mediate the transfer of client proteins from Hsp70 to Hsp90, and Cdc37 binds to kinase clients that inhibit Hsp90's ATPase activity. Co-chaperone Aha1 enhances Hsp90's ATPase activity by binding between HSP90's middle domain catalytic loop and the NTD nucleotide-binding site, facilitating the transition to a more stable closed transformation [72]. Unlike other chaperones, Hsp90 binds to partially folded intermediate conformations rather than to fully denatured proteins [73,74].
