Cryo EM study of membrane proteins complexes involved in inflammation diseases

SNIC 2022/5-520


SNIC Medium Compute

Principal Investigator:

Jesper Haeggstrom


Karolinska Institutet

Start Date:


End Date:


Primary Classification:

30401: Medical Biotechnology (focus on Cell Biology (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Secondary Classification:

30108: Cell and Molecular Biology



Cryo-EM is now used to generate structural models of membrane protein complexes (Kühlbrandt, 2014). Today, Cryo-EM is now considered as the best reliable alternative tool to collect high-resolution structural data of membrane protein complexes with sizes above 100 KDa through 3-D reconstruction. The study with our target complexes is feasible because most of our complexes are above 150 kDa. To understand in depth some of the key molecular mechanisms involved in the lipoxygenase pathways, the pure complexes CLP/5LO/FLAP/LTC4S or CLP/5LO/FLAP/ will be used for biochemical and structural analysis using either crystallography or Cryo-EM using the Cryo-EM facilities at SciLifeLab Our study also involved the understanding of the structural dynamics with computational analysis ((Brock et al, 2016), the processing of crystallographic data as well as electron microscopic data. The resources provided by the SNAC large is the perfect platform for us to efficiently establish the relation structure-function that will guide us toward the discovery of novel pharmaceutical therapy of diseases linked to the leukotriene formation and their activities. We also aim to structurally study the association of G-proteins with BLT1R, BLT2R, CysLT1R, CysLT2R, OXER1, and FPR2 G-PCRs in their active form with their respective agonists. In addition to atoms molecular dynamics simulations (MD) study that we have started in recent years, we are now strongly interested to use Cryo-Electron Microscopy (Cryo-EM) analysis to tackle our present scientific questions.