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Oligomerization of drug transporters:Forms,functions,and mechanisms

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Drug transporters are essential players in the transmembrane transport of a wide variety of clinical drugs.The broad substrate spectra and versatile distribution pattern of these membrane proteins infer their pharmacological and clinical significance.With our accumulating knowledge on the three-dimensional structure of drug transporters,their oligomerization status has become a topic of intense study due to the possible functional roles carried out by such kind of post-translational modification(PTM).In-depth studies of oligomeric complexes formed among drug transporters as well as their inter-actions with other regulatory proteins can help us better understand the regulatory mechanisms of these membrane proteins,provide clues for the development of novel drugs,and improve the therapeutic effi-cacy.In this review,we describe different oligomerization forms as well as their structural basis of major drug transporters in the ATP-binding cassette and solute carrier superfamilies,summarize our current knowledge on the influence of oligomerization for protein expression level and transport function of these membrane proteins,and discuss the regulatory mechanisms of oligomerization.Finally,we highlight the challenges associated with the current oligomerization studies and propose some thoughts on the pharma-ceutical application of this important drug transporter PTM.

Drug developmentDrug transportersOligomerizationProtein expressionProtein-protein interactionRegulatory mechanismStructural basisTransport function

Chunxu Ni、Mei Hong

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College of Life Sciences,South China Agricultural University,Guangzhou 510642,China

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms,South China Agricultural University,Guangzhou 510642,China

Natural Science Foundation of Guangdong Province,China国家自然科学基金国家自然科学基金

2022A1515010552U183210181373473

2024

10.1016/j.apsb.2024.01.007

药学学报(英文版)

药学学报(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.14(5)
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