Membrane Protein Structural Biology Group

Understanding membrane proteins linked to disease

The Membrane Protein Structural Biology Group works on structural and functional characterizing of membrane proteins that are essential for human health and highly attractive targets in the treatment of disease.

The overarching aim is to reveal the molecular principles and determinants of transport processes across cellular membranes for these proteins. To this end, we use a number of complementary techniques centered on X-ray crystallography and cryo-EM using the latest techniques to study structure-function-disease relationships of membrane proteins.

The group is based at the University of Copenhagen in Denmark and at Lund University in Sweden, where we work in close collaboration with the team of Karin Lindkvist.

Our research

Background

Membrane proteins are of critical importance to nearly every aspect of cell physiology, comprising about one-third of all proteins. Compared to soluble proteins, however, an understanding at the molecular-level for the membrane bound counterparts lags far behind. This lack of structural knowledge significantly impairs our understanding of the functions and mechanisms of these proteins, hereby preventing further applied, biomedical and biotechnological research.

Research focus

The focus of our group is eukaryotic and prokaryotic proteins that are linked to ion homeostasis and in particular transport of transition metals across cellular membranes. Our current targets include P-type ATPases of class IB (see figure) but also ion channels of various kinds. Underscoring the significance of these types of proteins, malfunctioning of the two human class IB P-type ATPases give rise to the severe Menkes’ and Wilson’s diseases, respectively.

Techniques

The structural studies are complemented with biochemical characterization in vivo (complementation) and in vitro, using for example ICP-MS, EXAFS, ITC, thermophoresis and molecular dynamics simulations in our own group and in association with a network of international partners.

Selection of recent publications

Purification of Functional Human TRP Channels Recombinantly Produced in Yeast. Zhang L, Wang K, Klaerke DA, Calloe K, Lowrey L, Pedersen PA, Gourdon P, Gotfryd K (2019). Cells. 8(2). pii: E148. doi: 10.3390/cells8020148.

Human adipose glycerol flux is regulated by a pH gate in AQP10. Gotfryd K, Mósca AF, Missel JW, Truelsen SF, Wang K, Spulber M, Krabbe S, Hélix-Nielsen C, Laforenza U, Soveral G, Pedersen PA, Gourdon P (2018). Nature Communications 9(1):4749.

Isolation and Characterization of Nanobodies against a Zinc-Transporting P-Type ATPase. Longhin E, Grønberg C, Hu Q, Duelli AS, Andersen KR, Laursen NS, Gourdon P (2018). Antibodies 7(4), 39