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Updated: Jan 10, 2026
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Characterization of Membrane Transporters by Heterologous Expression in E. coli and Production of Membrane Vesicles
Published on: December 31, 2019
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Substrate recognition diversity and transport dynamics of ABCC1
Panpan Sun1,2, Kexin Liu1,2, Linnan Zhang3
1National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Nature Communications
|November 25, 2025
Summary
This study reveals the structure and function of ABCC1, an important transporter protein. We uncovered how ABCC1 binds diverse substrates and identified a novel nucleotide release mechanism crucial for its transport activity.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- ABCC1 (ATP-binding cassette transporter, subfamily C, member 1) is a key transporter protein involved in drug resistance and physiological processes.
- It exports a wide range of endogenous and exogenous substrates, including anticancer drugs and glutathione conjugates.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying ABCC1's substrate recognition and transport dynamics.
- To provide high-resolution structural insights into ABCC1's functional states.
Main Methods:
- Cryo-electron microscopy (cryo-EM) to determine ten structures of ABCC1 in various functional states.
- Mutagenesis and functional assays to validate structural findings.
Main Results:
- ABCC1 possesses a flexible, bipartite substrate-binding pocket accommodating diverse molecules like glutathione (GSH) conjugates and cyclic dinucleotides.
- A substrate-releasing intermediate state revealed ATP-driven conformational changes and pocket reorganization during transport.
- A novel sequential nucleotide release mechanism was identified, with ADP releasing before ATP hydrolysis, priming the transporter for turnover.
Conclusions:
- The findings provide a comprehensive structural and mechanistic framework for ABCC1 function.
- Understanding ABCC1's molecular basis is crucial for developing targeted modulators for therapeutic applications.
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