20 June 2019

Second publication in Nature journal for Protein Analysis Group

Publication

For the second time in two months, the Protein Analysis Group is published in the world-renowned Nature journal.

Protein Analysis group photo

The published paper, entitled Substrate-induced conformational dynamics of the dopamine transporter, is the outcome of a collaboration project between the Protein Analysis group (lead by Prof. Kasper Rand) the Molecular Neuropharmacology group from the Department of Neuroscience, lead by Prof. Claus Løland.

The project is funded by an FP1 grant from Danmarks Frie Forskning.

In this work, we probe the global Na+- and dopamine-induced conformational dynamics of the wild-type dopamine transporter using hydrogen-deuterium exchange mass spectrometry. We identify Na+- and dopamine-induced changes in specific regions of the transporter, suggesting their involvement in protein conformational transitions. Furthermore, we detect ligand-dependent slow cooperative fluctuations of helical stretches in several domains of the transporter, which could be a molecular mechanism that assists in the transporter function. Our results provide a framework for understanding the molecular mechanism underlying the function of the key drug targets of the neurotransmitter:symporter (NSS) protein family. Our findings pave the way for future detailed studies into the transition path between transport states to fully elucidate the mechanism and regulation of such pharmaceutically relevant NSS proteins.

Abstract of the article in Nature Communications

You can read the whole paper on the Nature Communications website.

Read more about the first paper, published on April 11, 2019.

Find out more about the Protein Analysis Group and the Molecular Neuropharmacology Group.