The ABCG2/BCRP transporter and its variants – from structure to pathology

AbstractThe 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 humanABCG2 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 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.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: REVIEW Source Type: research