Expression, Function and Trafficking of the Human ABCG2 Multidrug Transporter Containing Mutations in an Unstructured Cytoplasmic Loop

• DOI: 10.20944/preprints202309.0514.v1
• Publication Date: 2023-09-08T00:20:35Z
• Authors: Orsolya Mózner; Boglarka Zámbó; Zsuzsanna Bartos; Anna Gergely; Kata Sára Szabó; Bálint Jezsó; Ágnes Telbisz; György Várady; László Homolya; Tamás Hegedűs; Balázs Sarkadi
• Keywords: Abcg2; Alanine; Transport protein

The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- endobiotics, contributes to cancer drug resistance development gout. In this work we have analyzed effects selected variants, residing structurally unresolved cytoplasmic region (a.a. 354-367) ABCG2, on function trafficking protein. A cluster four lysines (K357-360) phosphorylation threonine (T362) residue been previously suggested significantly affect cellular fate ABCG2. Here report that naturally occurring K360del variant cells increased plasma membrane expression accelerated trafficking. variable alanine replacements neighboring had no significant effect transport function, apical localization polarized has not altered by any these mutations. Moreover, contrast previous reports, found incompetent T362A, or mimicking T362E variants loop, measurable Molecular dynamics simulations indicated an mobility mutant with major core structure These results may help decipher potential unstructured within transporter.