Rasmussen Lab – University of Copenhagen

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CNS > Research > Section for Molecular and Cellular Neuroscience > Rasmussen Lab

Rasmussen Lab

The purpose of the research in my lab is to understand how G-protein coupled receptors (GPCRs) and neurotransmitter transporters function at the molecular level.

Specifically we are interested in

i) neurotransmitter-induced conformational changes in GPCRs and transporters and mechanisms behind their inhibition by antagonists;

ii) how GPCRs activate and discriminate between G protein subtypes;

iii) how GPCR function and trafficking behavior is influenced by the lipid environment and architecture. We are mainly working with the adenosine A2A receptor (A2A), the a2A and b2 adrenergic receptors (b2AR), the Gs and Gi proteins through which these GPCRs signal, and the serotonin transporter (SERT). We study these proteins in their purified state or reconstituted in nanodisc or liposomes using various biophysical techniques (protein crystallography, fluorescence spectroscopy, hydrogen-deuterium exchange mass spectrometry, CryoEM, NMR) and biochemical assays (radioligand binding and signalling assays).

To aid our investigations we have generated a number of camelid single chain antibody fragments (nanobodies) against the b2AR and G proteins and are working on obtaining nanobodies against the A2A and SERT. These nanobodies work as versatile tools to study the structure and function of these proteins in purified and reconstituted systems as well as conformational biosensors in live cells.

A future research goal is to develop a potential replacement therapy option for Parkinson’s disease (PD) using adeno-associated virus delivered nanobodies disrupting A2A function since long-term use of dopamine-replacing agents is associated with the development of motor complications in PD. 

Key publications last 10 years

  • DeVree B.T., Mahoney J.P., Vélez-Ruiz G.A., Rasmussen S.G.F.,.….Sunahara R.K., Allosteric coupling from G protein to the agonist binding pocket in GPCRs. Nature (2016) 535:182-6
  • Mathiesen S., Christensen S.M., Fung J.J., Rasmussen S.G.F.,.….Stamou D., High-content analysis of single proteoliposome composition used to assay quantitatively GPCR oligomerization. Nature Methods (2014) 1:931-4
  • Irannejad R., Tomshine J.C., Tomshine J.R., Chevalier M., Mahoney J.P., Steyaert J., Rasmussen S.G.F.,.….von Zastrow M. Conformational biosensors reveal GPCR signaling from endosomes. Nature (2013) 495:534-538
  • Rasmussen S.G.F.§, DeVree B.T.§,…..Kobilka B.K., Crystal Structure of the β2 Adrenergic Receptor-Gs Protein Complex. Nature (2011) 477:550-555.   §Authors contributed equally to this work
  • Chung K.Y§, Rasmussen S.G.F.§, Liu T. §,…..Sunahara R.K. Conformational changes in the G protein Gs by the β2 Adrenergic Receptor. Nature (2011) 477: 611-615.    §Authors contributed equally to this work
  • Rasmussen S.G.F. §, Choi H.J. §, Fung J.J.§,..….Kobilka B.K., Structure of an Nanobody-Stabilized Active State of the β2 Adrenoceptor, Nature (2011) 469:175-180.     §Authors contributed equally to this work
  • Westfield G.§, Rasmussen S.G.F.§, Su M. §, Dutta S. §,…...Skiniotis G., Structural Rearrangements of the Gas a-Helical Domain in the β2-adrenoceptor Gs Complex. Proc. Natl. Acad. Sci. USA. (2011) 108:16086-91.  §Authors contributed equally to this work

Overall publication metrics: Number of peer reviewed papers: 37; H-index: 29; i10-index: 34 Patents: 4