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Related Experiment Videos

Sequence of mdr3 cDNA encoding a human P-glycoprotein.

A M van der Bliek1, P M Kooiman, C Schneider

  • 1The Netherlands Cancer Institute, Department of Molecular Biology, Amsterdam.

Gene
|November 30, 1988
PubMed
Summary

Researchers sequenced the human mdr3 gene, revealing a protein similar to P-glycoproteins involved in multi-drug resistance (MDR). This suggests mdr3 may also function as an efflux pump.

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Area of Science:

  • Molecular Biology
  • Genetics

Background:

  • The mdr3 gene encodes a P-glycoprotein, a membrane protein family often overexpressed in multi-drug-resistant (MDR) cells.
  • P-glycoproteins are implicated in cellular drug efflux mechanisms.

Purpose of the Study:

  • To determine the complete nucleotide sequence of the human mdr3 gene.
  • To analyze the structural and functional implications of the mdr3 gene sequence.

Main Methods:

  • cDNA derived from liver RNA was used to determine the human mdr3 gene sequence.
  • Sequence analysis was performed to identify conserved domains and compare homology with related genes.

Main Results:

  • The human mdr3 gene sequence was determined, predicting a 140,000 Mr protein.

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  • The protein sequence shows two similar halves, each with hydrophobic segments potentially forming a membrane channel and nucleotide-binding sites characteristic of ATPases.
  • High sequence homology (approx. 80% conservation in transmembrane domains) was observed between mdr3 and mdr1 gene products, with evidence of gene conversion.

    • Conclusions:

    • The mdr3 gene product shares significant structural homology with the mdr1 gene product, suggesting a conserved function.
    • The findings indicate that mdr3 likely encodes an efflux pump with broad specificity, similar to mdr1, potentially contributing to drug resistance mechanisms.