The Role of Flexible Loops in Folding, Trafficking and Activity of Equilibrative Nucleoside Transporters. Academic Article uri icon

Overview

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 fine-tuning of transport regulation.

publication date

  • September 25, 2015

Research

keywords

  • Amino Acid Sequence
  • Cell Membrane
  • Equilibrative Nucleoside Transporter 1
  • Protein Folding
  • Sequence Deletion

Identity

PubMed Central ID

  • PMC4583308

Scopus Document Identifier

  • 84947790279

Digital Object Identifier (DOI)

  • 10.1074/jbc.M110.115758

PubMed ID

  • 26406980

Additional Document Info

volume

  • 10

issue

  • 9