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Related Concept Videos

ABC Transporters: Exporter01:31

ABC Transporters: Exporter

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ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
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ABC Transporters: Importer01:27

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ATP-binding cassette or ABC transporters are a class of ATP-driven pumps that hydrolyze ATP to move solutes across the membrane. They can be grouped into importers and exporters. While exporters are present in all domains of life, importers exist only in bacteria and some plants.
In bacteria, based on the number of transmembrane helices and the chemical nature of their substrates, the ABC importers can be divided into three types:
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Carrier-Mediated Transport01:06

Carrier-Mediated Transport

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Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...
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Drug Absorption Mechanism: Carrier-Mediated Membrane Transport01:19

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Certain large, lipid-insoluble drug molecules that resemble amino acids, peptides, or glucose, require specialized carrier proteins to facilitate their diffusion across cell membranes. This transport can occur through either facilitated diffusion, which does not require energy input, or active transport, which does require energy input.
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The Significance of Membrane Transport01:44

The Significance of Membrane Transport

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The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
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Membrane Transporters01:31

Membrane Transporters

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Transporters are essential membrane transport proteins with functions related to cell nutrition, homeostasis, communication, etc. Approximately 7% of all genes in the human genome code for transporters or transporter-related proteins.
Transporters are mainly composed of alpha-helices, built from bundles of ten or more helices traversing the plasma membrane. The solute-binding sites are located midway, where some of the helices are broken or distorted, making space for the binding site through...
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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
Summary

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.

Keywords:
ABC transportercancer therapymultidrug resistance (MDR)structure-based studies

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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.