ABCG2トランスポーターとは？

ABCG2 belongs to the ABC transporter superfamily and functions as a poly‐specific efflux pump. As it can transport a broad spectrum of substrates out of cells, ABCG2 is thought to alter the pharmacokinetics of drugs applied to treat certain diseases. (3D structure of the transporter ABCG2—What’s new? Br J Pharmacol. 2020 Apr; 177(7): 1485–1496. Published online 2020 Feb 11. doi: 10.1111/bph.14991)

ABCG2トランスポーターの構造

 In general, ABC transporters are built of two transmembrane domains (TMDs) with at least 12 membrane spanning α‐helices and two catalytic nucleotide binding domains (NBDs) facing the cytosol (Polgar et al., 2008). (3D structure of the transporter ABCG2—What’s new? Br J Pharmacol. 2020 Apr; 177(7): 1485–1496. Published online 2020 Feb 11. doi: 10.1111/bph.14991)

ABCG2トランスポーターへのATP結合と構造変化

To fully bind an ATP molecule, a dimerization of the two NBDs is necessary, as not all of the structural elements within a single NBD can be arranged around the ATP molecule. Therefore, two ATP molecules glue two NBDs together using the missing structural elements from the opposing NBD in a complementary fashion (Walker A, Q‐loop, Walker B, and H‐loop from NBD1; C‐signature and D‐loop from NBD2). ATP binding‐induced conformational changes (two open NBDs to a dimer of closed NBDs) are thought to take place in order to provide the energy for substrate transport through the translocation pathway within the TMD (Manolaridis et al., 2018; McDevitt et al., 2008). (3D structure of the transporter ABCG2—What’s new? Br J Pharmacol. 2020 Apr; 177(7): 1485–1496. Published online 2020 Feb 11. doi: 10.1111/bph.14991)