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Leucine heptad motifs within transmembrane domains affect function and oligomerization of human organic anion transporting polypeptide 1B1.

Authors
  • Ni, Chunxu1
  • Wang, Xuyang1
  • Chen, Jie1
  • Xu, Su1
  • Ye, Wenjing1
  • Hong, Mei2
  • 1 College of Life Sciences, South China Agricultural University, Guangzhou, China. , (China)
  • 2 College of Life Sciences, South China Agricultural University, Guangzhou, China; Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, South China Agricultural University, Guangzhou, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Biochimica et biophysica acta. Biomembranes
Publication Date
Jan 08, 2021
Volume
1863
Issue
4
Pages
183554–183554
Identifiers
DOI: 10.1016/j.bbamem.2021.183554
PMID: 33428894
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Organic anion transporting polypeptides (OATPs) are transmembrane proteins responsible for the uptake of a wide range of endogenous compounds and clinically important drugs. The liver-specific OATP1B1 serves crucial roles in the removal of many orally administered drugs. The proper function of the transporter hence is essential for the pharmacokinetics of various therapeutic agents. Membrane proteins tend to form oligomers that are important for their stability, targeting and/or interactions with the substrates. Previous study in our laboratory revealed that OATP1B1 may form homo-oligomers and that a GXXXG motif localized at transmembrane domain 8 (TM8) may affect its oligomerization. In the current study, three short-form leucine heptad repeats within the transmembrane domains of OATP1B1 were investigated. It was found that the disruption of leucine heptad repeats within TM3 dramatically reduced the uptake function and protein-protein association of OATP1B1; while within TM8, only L378 is essential for the function of OATP1B1 and alanine replacement of L378 exhibited no effect on the oligomerization. The fragmental expression of TM3 interfered with the association of OATP1B1 homo-oligomers as well as its association with OATP1B3, which is also selectively expressed at human hepatocytes, suggesting that the region may be shared by both transporters for their protein-protein interactions. Copyright © 2021 Elsevier B.V. All rights reserved.

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