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.
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.
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.
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
Part of the research theme
Letter in Nature
Pontus Gourdon’s research is in Nature. Read the publication ‘Structure and mechanism of
Zn(II)-transporting P-type ATPases’ in Nature.
Review in Biochemistry
Read our recent publication 'Structure and Function of Cu(I)- and Zn(II)-ATPases.'
Research article in PLos Biology
Our recent paper ‘Crystal Structure of an Ammonia-Permeable Aquaporin’