Ion Modulation in Secondary Transporters
Abstract
Molecular transport across the cell membrane is an important and highly regulated process. Secondary transporters are a large family of integral membrane proteins responsible for mediating molecular exchange. Pre-existing ion gradients are utilized to drive secondary transport. Our focus was on the solute carrier (SLC) family of secondary transporters, specifically those that utilize Na+ to drive transport. The SLC family can be further classified as a sodium substrate symporter (SSS). Specifically, we focused on the human serotonin and dopamine transporters (SLC6) and iodide symporters (SLC5). The sodium electrochemical potential is coupled to the energetically unfavourable transport of the substrate. This yields a net favourable translocation of the substrate and co-transported ions. Little structural information is available on the SSS family transporters and even less when only the human variants are considered. This prompted an attempt to predict human protein structures using the available data from bacterial homologues to fill the knowledge gap. The methodology was based on the X-ray structures of the leucine transporter (LeuT) and sodium galactose transporter (vSGLT). Through our structural alignments we were able to identify the ion binding sites. With the help of Glide docking software, we successfully identified substrate and inhibitors binding sites. Molecular dynamics were used to simulate biologically relevant systems and find the forces driving substrate and ion binding. Our computational biochemistry approach has proven to be a reliable method to study the transport and substrate interactions. In addition, our collaborative efforts successfully merged theoretical and experimental science.
Description
Keywords
Biology, Bioinformatics, Microbiology, Neuroscience, Biophysics, Biophysics--Medical, Mental Health, Pharmacology, Chemistry--Pharmaceutical
Citation
Zdravkovic, I. (2016). Ion Modulation in Secondary Transporters (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/26671