ATP-dependent thermostabilization of human P-glycoprotein (ABCB1) is blocked by modulators.

ABSTRACT: P-glycoprotein (P-gp), an ATP-binding cassette transporter associated with multidrug resistance in cancer cells, is capable of effluxing a number of xenobiotics as well as anticancer drugs. The transport of molecules through the transmembrane (TM) region of P-gp involves orchestrated conformational changes between inward-open and inward-closed forms, the details of which are still being worked out. Here, we assessed how the binding of transport substrates or modulators in the TM region and the binding of ATP to the nucleotide-binding domains (NBDs) affect the thermostability of P-gp in a membrane environment. P-gp stability after exposure at high temperatures (37-80°C) was assessed by measuring ATPase activity and loss of monomeric P-gp. Our results show that P-gp is significantly thermost

SUBMITTER: Lusvarghi S 

PROVIDER: S-EPMC7404625 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature