Heat shock protein (HSP)A (Hsp70, large HSP) and HSPC (Hsp90, GP96) each possess two major domains including a nucleotide (ATP, ADP) binding domain and a polypeptide (substrate) binding domain. When ATP binds to the HSP, the polypeptide-binding domain opens and cargo dissociates. When ADP binds to the nucleotide-binding domain, polypeptide cargo is bound and in this form HSP may capture and chaperone tumor antigens. These two domains, although similar in function, may differ considerably between individual HSPs. Pi: Phosphate; S: Substrate.