Identification of tyrosine residues critical for the function of an ion-coupled multidrug transporter

Dvir Rotem, Sonia Steiner-Mordoch, Shimon Schuldiner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Aromatic residues may play several roles in integral membrane proteins, including direct interaction with substrates. In this work, we studied the contribution of tyrosine residues to the activity of EmrE, a small multidrug transporter from Escherichia coli that extrudes various drugs across the plasma membrane in exchange with protons. Each of five tyrosine residues was replaced by site-directed mutagenesis. Two of these residues, Tyr-40 and Tyr-60, can be partially replaced with hydroxyamino acids, but in the case of Tyr-40, replacement with either Ser or Thr generates a protein with modified substrate specificity. Replacement of Tyr-4 with either Trp or Phe generates a functional transporter. A Cys replacement at this position generates an uncoupled protein; it binds substrate and protons and transports the substrate downhill but is impaired in uphill substrate transport in the presence of a proton gradient. The role of these residues is discussed in the context of the published structures of EmrE.

Original languageAmerican English
Pages (from-to)18715-18722
Number of pages8
JournalJournal of Biological Chemistry
Issue number27
StatePublished - 7 Jul 2006


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