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Multidrug resistance-associated protein 4 is a bile transporter of Clonorchis sinensis simulated by in silico docking

Fuhong Dai1, Won Gi Yoo1, Ji-Yun Lee1

  • 1Department of Medical Environmental Biology, Chung-Ang University College of Medicine, Seoul, 06974, South Korea.

Parasites & Vectors
|November 22, 2017
PubMed
Abstract

Insights

Multidrug resistance-associated protein 4 (MRP4) in Clonorchis sinensis is a bile transporter crucial for parasite survival. CsMRP4 facilitates bile acid transport, with higher mRNA levels in early life stages and specific tissue localization.

Area of Science:

  • Parasitology
  • Molecular Biology
  • Biochemistry

Background:

  • Multidrug resistance-associated protein 4 (MRP4) is an ATP-binding cassette transporter involved in efflux of substrates like bile acids.
  • Clonorchis sinensis resides in bile ducts, necessitating mechanisms to manage potentially toxic bile acid accumulation.
  • Bile transporters are essential for C. sinensis to prevent cellular damage from bile juice.

Purpose of the Study:

  • To clone and characterize the MRP4 transporter from Clonorchis sinensis (CsMRP4).
  • To investigate the structural and functional properties of CsMRP4 in relation to bile acid transport.
  • To determine the expression patterns and localization of CsMRP4 in C. sinensis.

Main Methods:

  • Cloning of CsMRP4 cDNA and sequence analysis.
  • Phylogenetic analysis to determine subfamily classification.
  • Homology modeling for tertiary structure generation.
  • Molecular docking simulations with bile acids.
  • Quantitative analysis of CsMRP4 mRNA expression.
  • Immunolocalization studies using specific antibodies.

Main Results:

  • CsMRP4 cDNA encodes a 1469-amino acid protein belonging to the MRP/SUR/CFTR subfamily.
  • Homology modeling revealed a typical ABC transporter structure with membrane-spanning and nucleotide-binding domains.
  • Docking simulations indicated CsMRP4 transports bile acids via an internal cavity.
  • CsMRP4 mRNA expression was higher in metacercariae than adult worms.
  • Immunolocalization showed CsMRP4 concentrated in mesenchymal tissues and suckers of both life stages.

Conclusions:

  • The study identified and characterized CsMRP4, a key bile transporter in C. sinensis.
  • Findings provide insights into the structural basis of bile acid transport by CsMRP4.
  • The results highlight the role of CsMRP4 in parasite survival and offer targets for further research.
Keywords:
ABCC4Bile transporterClonorchis sinensisLocalizationMRP4Structure

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