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Amino‐terminal region plays an important role in transport function of human organic anion transporting polypeptide 1B1
Author(s) -
Hong Mei,
Chen Jie,
Xiang Zhaojian,
Fang Zihui,
Ni Chunxu
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.693.11
Subject(s) - transporter , organic anion transporting polypeptide , transmembrane domain , alanine , transmembrane protein , alanine scanning , solute carrier family , function (biology) , transport protein , organic anion transporter 1 , biochemistry , amino acid , chemistry , mutant , biology , microbiology and biotechnology , gene , receptor , mutagenesis
Objective The 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. Methods Alanine‐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. Results Two 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. Conclusions The N‐terminus region of OATP1B1 is important for maintaining proper function and protein expression level of the transporter. Support or Funding Information This 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 .