NIH Investigator Dr. Lucy Forrest, National Institute of Neurological Disorder and Stroke (NINDS), NIH, Maryland, USA

Symmetry and Sodium in Secondary Transporters

Sodium-coupled transporters are responsible for the movement of a wide range of solutes across cell membranes. Recent successes in structural biology have provided seminal insights into their architecture and mechanisms, including the observation that a majority of the structural folds contain within them internal repeated elements whose transmembrane topologies are inverted with respect to the membrane. Nevertheless, significant gaps in our understanding remain. For structures that have been determined, the resolution leaves doubt as to the location of the coupling ion binding sites. And, structures for other transport protein families remain to be determined. New understanding of the presence of structural repeats has helped in both of these challenges. I will show how using novel theoretical and computational strategies we have predicted the locations of sodium binding sites, and predicted the fold and binding sites of a sodium-coupled phosphate transporter (see figure) by first identifying structurally repeated elements. In both cases, experimental support of the hypotheses from collaborators will be shown. Similar strategies are likely to be useful in answering related questions in the myriad of transporter proteins yet to be structurally characterized.