Premium
The ABCG2/BCRP transporter and its variants – from structure to pathology
Author(s) -
Sarkadi Balázs,
Homolya László,
Hegedűs Tamás
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13947
Subject(s) - abcg2 , transporter , atp binding cassette transporter , biology , microbiology and biotechnology , function (biology) , solute carrier family , multidrug resistance associated proteins , endocytosis , biochemistry , gene , receptor
The ABCG2 protein has a key role in the transport of a wide range of structurally dissimilar endo‐ and xenobiotics in the human body, especially in the tissue barriers and the metabolizing or secreting organs. The human ABCG2 gene harbors a high number of polymorphisms and mutations, which may significantly modulate its expression and function. Recent high‐resolution structural data, complemented with molecular dynamic simulations, may significantly help to understand intramolecular movements and substrate handling, as well as the effects of mutations on the membrane transporter function of ABCG2. As reviewed here, structural alterations may result not only in direct alterations in drug binding and transporter activity, but also in improper folding or problems in the carefully regulated process of trafficking, including vesicular transport, endocytosis, recycling, and degradation. Here, we also review the clinical importance of altered ABCG2 expression and function in general drug metabolism, cancer multidrug resistance, and impaired uric acid excretion, leading to gout.