How are protein clients released from Hsc70?

A nucleotide exchange factor (NEFs eg. BAG-1,2) binds the Hsc70: client complex and removes ADP from the nucleotide-binding site of Hsc70. This promotes NUCLEOTIDE EXCHANGE, allowing entry of ATP into the nucleotide binding site of Hsc70. Hsc70:ATP adopts an OPEN conformation, releasing the client protein.