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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

ABC Transporters: Importer

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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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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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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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Glucose Transporters01:27

Glucose Transporters

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Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
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The ABCG2 Transporter Affects Plasma Levels, Tissue Distribution and Milk Secretion of Lumichrome, a Natural Derivative of Riboflavin.

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Author Spotlight: A Bicelle Crystallization Setup for ABC Transporter Membrane Proteins to Advance Drug Development
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Author Spotlight: A Bicelle Crystallization Setup for ABC Transporter Membrane Proteins to Advance Drug Development

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ABCG2 Transporter: From Structure to Function-Current Insights and Open Questions.

Laura Álvarez-Fernández1, Alicia Millán-García1, Gracia Merino1

  • 1Department of Biomedical Sciences-Physiology, Faculty of Veterinary Medicine, Instituto de Desarrollo Ganadero y Sanidad Animal (INDEGSAL), University of León, Campus de Vegazana s/n, 24071 León, Spain.

International Journal of Molecular Sciences
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PubMed
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The ATP-binding cassette transporter ABCG2 is vital for drug resistance. This review synthesizes structural biology advances to clarify its transport mechanism, crucial for developing new therapies.

Keywords:
ABCG2conformationstructuretransport

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Area of Science:

  • Structural biology
  • Molecular biology
  • Biochemistry

Background:

  • ABCG2 (ATP-binding cassette sub-family G member 2) is a critical transporter implicated in multidrug resistance and physiological functions.
  • While cryo-electron microscopy (cryo-EM) has revealed multiple ABCG2 structures, a high-resolution X-ray crystallographic structure remains elusive, hindering a complete understanding of its transport cycle dynamics.

Purpose of the Study:

  • To review recent advancements in ABCG2 structural biology.
  • To highlight ongoing controversies and unresolved questions regarding ABCG2 function.
  • To propose future directions for integrating structural and functional data to elucidate ABCG2's mechanism.

Main Methods:

  • Compilation and synthesis of existing literature on ABCG2 structural biology.
  • Analysis of cryo-electron microscopy (cryo-EM) data and comparison with other structural information.
  • Discussion of functional studies related to ABCG2 transport and regulation.

Main Results:

  • Recent cryo-EM studies have provided significant insights into ABCG2 conformational states.
  • Key aspects of the ABCG2 transport cycle remain unresolved due to the lack of high-resolution X-ray structures.
  • A multidisciplinary approach is essential for a comprehensive understanding of ABCG2.

Conclusions:

  • Integrating diverse structural and functional data is crucial for deciphering the complex ABCG2 transport mechanism.
  • Detailed structural insights are vital for identifying novel ABCG2 substrates and designing targeted inhibitors.
  • Advancements in understanding ABCG2 hold significant potential for therapeutic development, particularly in overcoming multidrug resistance.