Structure and Function in serotonin transporter (SERT)
Several projects in the lab are concerned with understanding aspects of transporter function, including binding sites for substrate and symported ions. Shown here is a model for the Cl- binding site in SERT, based on studies both in SERT and the bacterial homolog TnaT. See Tavoulari et al, 2011.
Regulation of SERT by PKG
A SERT mutation found in several unrelated families are associated with several psychiatric disorders. We found that the mutation led to altered regulation of cGMP-dependent activation of SERT activity. We are continuing to investigate the signaling pathway leading to SERT activation. Shown at left is a model of SERT (blue) and PKG (orange) with the phosphorylated threonine in the active site of the kinase (model created by Lucy R. Forrest, MPI Biophysics, Frankfurt).
Prokaryotic SERT homologues
We are using proteins such as LeuT and TnaT as model systems to study structure-function relationships in the larger family of transporters related to SERT. Shown here are residues around the binding site for Na+ and leucine in LeuT. Na1 (blue) is flanked on each side by Na2 (blue) and the completely ionized Glu-290 from TM7, by leucine (yellow) and by Asn-27 (TM1).