The role of flexible loops in folding, trafficking and activity of equilibrative nucleoside transporters

Jaya Aseervatham, Lucky Tran, Khaled Machaca, Olga Boudker

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Equilibrative nucleoside transporters (ENTs) are integral membrane proteins, which reside in plasma membranes of all eukaryotic cells and mediate thermodynamically downhill transport of nucleosides. This process is essential for nucleoside recycling, and also plays a key role in terminating adenosine-mediated cellular signaling. Furthermore, ENTs mediate the uptake of many drugs, including anticancer and antiviral nucleoside analogues. The structure and mechanism, by which ENTs catalyze trans-membrane transport of their substrates, remain unknown. To identify the core of the transporter needed for stability, activity, and for its correct trafficking to the plasma membrane, we have expressed human ENT deletion mutants in Xenopus laevis oocytes and determined their localization, transport properties and susceptibility to inhibition. We found that the carboxyl terminal trans-membrane segments are essential for correct protein folding and trafficking. In contrast, the soluble extracellular and intracellular loops appear to be dispensable, and must be involved in the finetuning of transport regulation.

Original languageEnglish
Article numbere0136779
JournalPLoS One
Volume10
Issue number9
DOIs
Publication statusPublished - 25 Sep 2015

Fingerprint

Nucleoside Transport Proteins
nucleosides
transporters
Nucleosides
Cell membranes
Cell Membrane
Cell signaling
Membranes
Protein folding
Protein Folding
Xenopus laevis
Recycling
Eukaryotic Cells
Protein Transport
Adenosine
Transport properties
plasma membrane
Oocytes
Antiviral Agents
Membrane Proteins

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

The role of flexible loops in folding, trafficking and activity of equilibrative nucleoside transporters. / Aseervatham, Jaya; Tran, Lucky; Machaca, Khaled; Boudker, Olga.

In: PLoS One, Vol. 10, No. 9, e0136779, 25.09.2015.

Research output: Contribution to journalArticle

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