Projects

Structure and Function in serotonin transporter (SERT)

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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

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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

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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).