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Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
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Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System

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A Structure-Based View on ABC-Transporter Linked to Multidrug Resistance

Jiahui Huang1, Gerhard F Ecker1

  • 1Department of Pharmaceutical Sciences, University of Vienna, 1140 Vienna, Austria.

Molecules (Basel, Switzerland)
|January 21, 2023
PubMed

Insights

This review details ATP-binding cassette (ABC) transporter structures, crucial for understanding and overcoming multidrug resistance (MDR) in cancer. Structure-based studies, including AI predictions, offer new insights into these vital transmembrane proteins.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Pharmacology

Background:

  • ATP-binding cassette (ABC) transporters are key transmembrane proteins involved in numerous physiological processes.
  • Overexpression of ABC transporters in cancer cells leads to multidrug resistance (MDR), a major challenge in chemotherapy.
  • Understanding the structure of ABC transporters is critical for developing strategies to inhibit their function.

Purpose of the Study:

  • To provide a comprehensive overview of the structural aspects of the ABC transporter superfamily.
  • To summarize experimentally determined structures and recent structure-based studies.
  • To discuss the role of artificial intelligence (AI), specifically AlphaFold-2, in predicting ABC transporter structures.

Main Methods:

  • Review of experimentally solved structures obtained through advanced electron microscopy techniques.
  • Analysis of recent structure-based research on ABC transporters.
  • Inclusion and discussion of AI-driven structural predictions, such as those from AlphaFold-2.

Main Results:

  • A rapid increase in experimentally determined ABC transporter structures.
  • Emerging insights from structure-based studies into transporter mechanisms and functions.
  • Demonstration of AI's potential in generating accurate structural models for this protein superfamily.

Conclusions:

  • Structural information is pivotal for understanding ABC transporter mechanisms and overcoming MDR.
  • Advanced imaging and AI-based predictions are significantly advancing the field of ABC transporter structural biology.
  • Future research leveraging structural data holds promise for novel therapeutic strategies against cancer MDR.
Keywords:
ABC transportercancer therapymultidrug resistance (MDR)structure-based studies

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