Amino‐terminal region plays an important role in transport function of human organic anion transporting polypeptide 1B1

Abstract

ObjectiveThe family of organic anion transporting polypeptides (OATPs, gene symbol SLCO) mediates sodium‐independent transport of a wide variety of endogenous and exogenous compounds. OATPs are considered as key players in drug absorption, distribution and excretion due to their broad substrate specificity, wide tissue distribution and involvement in drug‐drug interactions. OATP1B1 is specifically located at the basolateral membrane of human hepatocytes and serves a crucial role in drug clearance from the body. Previous studies have shown that transmembrane domains (TMs) of OATP1B1 are essential structural features for proper function of the transporter.MethodsAlanine‐scanning of the putative transmembrane domain 1 and truncation of the N‐terminus of OATP1B1 were carried out, and the uptake function and protein expression of mutants were analyzed.ResultsTwo positively charged amino acid residues, K41 and K49, were identified to be important for uptake function of the transporter protein. Alanine substitution of K41 altered substrate binding at the high affinity component; while K49A exhibited increased Km value at the low affinity site. In addition, our study of the N‐terminal residues of OATP1B1 found out that residues ranging from 19–27 are essential for protein stability and uptake function of the transporter protein.ConclusionsThe N‐terminus region of OATP1B1 is important for maintaining proper function and protein expression level of the transporter.Support or Funding InformationThis work was supported by the National Natural Science Foundation of China Grants [81373473] to Mei Hong.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.