During her PhD studies, Caroline researched  the three-dimensional structures of membrane transporters from the SLC6 and SLC12 families. Caroline used X-ray crystallography to investigate the binding site specificity and promiscuity of MhsT, a bacterial homologue of SLC6 transporters with a broad specificity for hydrophobic amino acids (ranging from L-valine to L-tryptophan). Six crystal structures of MhsT in complex with its substrates identified important rearrangements within the binding pocket important for recognition, accommodation and transport of the disparately sized substrates. Additionally, Caroline determined a cryo-EM structure of the human NKCC1 transporter from the SLC12 family. The structure allowed for analysis of substrate specificity, ion coupling and interfacial binding.

The new research findings contribute to the understanding of SLC6 and SLC12 transporters containing a common LeuT-fold. Despite low sequence identities between the two families, the study reveals surprising common features and structural elements not identified before.

The PhD study was completed at Molecular Biology and Genetics (MBG), Faculty of Natural Sciences, Aarhus University.

This summary was prepared by the PhD student.

Time: Friday, 25 June at 13.15  
Place: The PhD defence will be held online. To receive a link to the event, please send an e-mail to Karen Bech-Pedersen: karenb@mbg.au.dk. 
Title of PhD thesis: Structural studies of LeuT-fold transporters: 1) Investigation of the binding site specificity and promiscuity of the prokaryotic multihydrophobic amino acid transporter, MhsT. 2) Towards a cryo-EM structure of cation:chloride co-transporters.

Contact information: Caroline Marie Teresa Neumann, caroline@mbg.au.dk , tel.: +45 81122728.

Members of the assessment committee:

Professor David Drew, Department of Biochemistry and Biophysics, Stockholm University, Sweden

Associate Professor Osman Asghar Mirza, Department of Drug Design and Pharmacology, University of Copenhagen, Denmark

Professor Finn Skou Pedersen (chairman), Department of Molecular Biology and Genetics, Aarhus University, Denmark

Main supervisor:
Professor Poul Nissen, Department of Molecular Biology and Genetics, Aarhus University, Denmark

Co-supervisor:
Professor Robert Fenton, Department of Biomedicine, Aarhus University, Denmark

Language: The PhD dissertation will be defended in English

The defence is public.
Due to the coronavirus situation, the PhD thesis will not be available for reading at the offices of the PhD administration. Instead, interested parties may send an e-mail to gradschool.nat@au.dk to receive a digital copy of the PhD thesis. Please note, it may in certain cases be necessary to make an individual arrangement to read the PhD thesis.