Mechanistic aspects of sodium-binding sites in LeuT-like fold symporters

Camilo Perez; Christine Ziegler

doi:10.1515/hsz-2012-0336

Article

Mechanistic aspects of sodium-binding sites in LeuT-like fold symporters

Camilo Perez and Christine Ziegler

Published/Copyright: January 28, 2013

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From the journal Biological Chemistry Volume 394 Issue 5

Abstract

Secondary active transporters are of paramount biological impact in all living cells, facilitating the movement of many different substrates across the membrane against a concentration gradient. The uphill transport of one substrate is coupled to the downhill transport of another and driven by the electrochemical gradient. In the last decade, an increasing number of atomic structures of secondary transporters have been reported, confirming a very fundamental mechanistic concept known as the alternating-access cycle. The wealth of structures of transporters sharing the so-called LeuT-like fold that is characterized by two five-transmembrane-helix repeats sharing a 2-fold inverted pseudo symmetry has raised big hopes to finally describe alternating access on a molecular level. Although comparing the individual transporter states of different LeuT-like fold transporters revealed striking similarities, the coupling process, which represents the heart of secondary transport, is far from being understood. Here, we review the structural, functional, and biophysical validation of sodium-binding sites in four different LeuT-like fold transporters. The conservation of sodium sites is discussed in light of their role as key elements connecting symmetry-related structural domains, which are involved in substrate translocation. Moreover, we highlight their crucial roles in conformational changes of LeuT-like fold transporters and their implication on a unifying mechanism in secondary transport.

Keywords: alternating-access cycle; ion coupling; LeuT-like fold; secondary transporter; sodium binding; structure

Corresponding author: Christine Ziegler, Max Planck Institute of Biophysics, Structural Biology Department, Max-von-Laue-Strasse 3, D-60438 Frankfurt (Main), Germany; and Faculty of Biology and Preclinical Medicine, University of Regensburg, Universitätstraße 31, D-93053 Regensburg, Germany

Received: 2012-11-26

Accepted: 2013-1-24

Published Online: 2013-01-28

Published in Print: 2013-05-01

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Articles in the same Issue

https://doi.org/10.1515/hsz-2012-0336

Keywords for this article

alternating-access cycle; ion coupling; LeuT-like fold; secondary transporter; sodium binding; structure