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Structural studies on the substrate promiscuity of a bacterial SLC6 homolog

PhD defence, Thursday 8 December 2016. Dorota Focht

2016.12.07 | Emilie Marie Niebuhr Aagaard

Date Thu 08 Dec
Time 14:15 17:00
Location Building 3133, Conference room, 3rd floor, Department of Molecular Biology and Genetics, Gustav Wieds Vej 10 C, Aarhus University, 8000 Aarhus C.

During her studies, Dorota worked on the bacterial homologue of human neurotransmitter:sodium symporters (NSS), MhsT from Bacillus halodurans, which carries out the uptake of hydrophobic amino acids. Furthermore, MhsT’s broad substrate specificity (ranging from L-valine to L-tryptophan) resembles properties of the human amino acid transporters (AAT) from the SLC6 family of proteins, which also contains NSS. Dorota used protein X-ray crystallography in combination with in vivo uptake assays to determine the structural elements of the substrate binding site, which are essential in substrate recognition and binding by MhsT. Several crystal structures of the transporter, obtained in complex with various substrates, have captured the structural rearrangements within the binding site. The observed changes seem to compensate for differences between the particular amino acids, and allow for transport activity of the protein to be maintained.

The new research findings expand our knowledge on the transport mechanism of NSS and AAT proteins, whose malfunctions are involved in pathogenesis of severe neurological and systemic diseases.

The PhD degree was completed at the Department of Molecular Biology and Genetics, Science and Technology, Aarhus University.

This résumé was prepared by the PhD student.

When: Thursday 8 December 2016 at 14.15
Where: Building 3133, Conference room, 3rd floor, Department of Molecular Biology and Genetics, Gustav Wieds Vej 10 C, Aarhus University, 8000 Aarhus C.
Title of dissertation: Structural studies of the membrane transport proteins: the fungal plasma membrane ATPase – Pma1 and the bacterial NSS member– MhsT.
Contact information: Dorota Focht, e-mail: dofo@mbg.au.dk
Members of the assessment committee:

Professor Baruch Kanner, Faculty of Medicine, The Hebrew University of Jerusalem, Israel
Assoc. Professor Claus Juul Løland, Department of Neuroscience and Pharmacology, Copenhagen University, Denmark
Professor Finn Skou Pedersen (chair), Department of Molecular Biology and Genetics, Aarhus University
Main supervisor:
Professor Poul Nissen, Department of Molecular Biology and Genetics, Aarhus University
Language: The PhD dissertation will be defended in English.

The defence is public.
The dissertation is available for reading at the Graduate School of Science and Technology/GSST, Ny Munkegade 120, building 1520, rooms 128-134, 8000 Aarhus C.

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