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Staff photo Elisabeth Sauer-Eriksson

Elisabeth Sauer-Eriksson

Biological macromolecular crystallography

Works at

Affiliation
Location
KB.E4, Linnaeus väg 10, (rum: 4.07.02) Umeå universitet, 901 87 Umeå

Elisabeth Sauer-Eriksson is a structural biologist who studies structure-function relationships of RNA-RNA and RNA protein interactions. She also studies amyloidformation, and molecular mechanisms  behind host-pathogen interactions. The aim with the latter project is to aid discovery of new and improved drug candidates against infectious disease pathogens. Her group uses X-ray crystallography, chemical biology, and other in vitro biochemical and biophysical methods for their studies. 

Projects:

For more information see also the Integrated Structural Biology homepage

1) Amyloid-forming proteins
Transthyretin (TTR), Amyloid-beta-peptide, and medin are three examples of amyloid-forming protein, which we study in the lab. They belong to a group of over 20 proteins that to cause disease by the formation of insoluble fibrils called amyloids. The human tetrameric thyroid-binding protein TTR is associated with two medical disorders: familial amyloidotic polyneuropathy (FAP) caused by mutations within the protein, and senile systemic polyneuropathy (SSA) that involves the native protein. FAP is prevalent in the northern parts of Sweden, where it is sometimes also referred to as "Skelleftesjukan". Amyloidosis involves structural changes within the amyloidogenic protein. The nature of these changes is currently unknown but of utmost importance since it can provide vital clues that will help the identification of substances that can inhibit the formation of TTR amyloid.

2) The signal recognition particle (SRP)
SRP is a RNA-protein complex needed for the transfer of proteins through the endoplasmic reticulum in eukaryotic cells and plasma membranes in prokaryotic cells. It is absolutely essential for survival and found in all three kingdoms of life. We have made steadily progress toward the elucidation of structural states of SRP in assembly and function. In recent years we solved structures of the SRP RNA in its free form as well as in complex with its different protein partners. Together with a number of other structures of various SRP proteins, these structures provide new insights into the mechanisms of SRP activity, leading toward a better understanding of protein trafficking by this elegant pathway.

3) Carbonic anhydrases (CA)
CAs catalyse the conversion of carbon dioxide to bicarbonate and water. They are divided into four classes that share no structural homology, of which plant CA belongs to the beta-CA family. Members of the CA family are therefore good examples of convergent evolution where structurally unrelated proteins have evolved to perform the same function. Most of the CAs are extremely fast enzymes with a catalytic turn-over rate of 106/s. We are structurally and functionally characterizing several members of the alpha- and beta-family.

4) Proteins with crucial roles in host-pathogen interactions
Within this project we pursue several collaborative projects with colleagues here at Umeå University. The main theme for these collaborations is bacterial infection, and our work is on structural characterization of proteins that play crucial roles in host-pathogen interactions.

4a) Design of inhibitors for the master regulatory protein PrfA in Listeria monocytogenes.

Due to increased antibiotic resistance, new types of antibacterial agents are urgently needed. An alternative to the classical type of antibiotics are drugs inhibiting specific virulence properties of pathogenic bacteria. Almost all virulence genes in the human pathogen L. monocytogenes are controlled by the transcriptional activator PrfA, a member of the Crp/Fnr family of regulators. Jörgen Johansson and Fredrik Almqvist, from UmU, have identified ring-fused 2-pyridone molecules that, at low micromolar concentrations, attenuate L. monocytogenesinfectivity by reducing the expression of virulence genes, yet without compromising bacterial growth. These inhibitors bind PrfA and decrease its affinity toward the consensus DNA binding site. Our structural characterization reveals that the lead inhibitor binds within a hydrophobic pocket located between the C- and N-terminal domains of PrfA where it interacts with residues important for PrfA activation (Fig. 1, Good, et al, Cell Chem Biol. 2016,23(3):404-14.). Modified ligands are now being synthesized, tested for improved antivirulence properties, and subjected for structural studies. The PrfA-inhibitor structure is furthermore an excellent basis for our on-going investigation of other members of the Crp family as targets for antivirulence based therapeutics.

4b) Structural basis for glutathione-mediated activation of the virulence regulatory protein PrfA in Listeria.

It had been proposed that glutathione (GSH) could fulfill the function of PrfA activation. We determined the crystal structures of PrfA in complex with GSH and in complex with GSH and its cognate DNA, the hly operator PrfA box motif (Fig.2). Combined these structures reveal the structural basis for a GSH-mediated allosteric mode of activation of PrfA in the cytosol of the host cell (Hall et al., 2016 PNAS). More studies are pursued to further elucidate the molcular mechanism behind PrfA activiation

Journal of Bacteriology, American Society for Microbiology 2020, Vol. 202, (11)
Hansen, Sabine; Hall, Michael; Grundström, Christin; et al.
Biochemistry, American Chemical Society (ACS) 2020, Vol. 59, (38) : 3570-3581
Rogne, Per; Dulko-Smith, Beata; Goodman, Jack; et al.
Biophysical Journal, Cell Press 2020, Vol. 118, (3) : 193A-193A
Rogne, Per; Sauer-Eriksson, Elisabeth; Sauer, Uwe H.; et al.
Cell reports, Elsevier 2019, Vol. 26, (7) : 1815-1827
Krypotou, Emilia; Scortti, Mariela; Grundström, Christin; et al.
Biochemistry, American Chemical Society (ACS) 2019, Vol. 58, (32) : 3408-3412
Rogne, Per; Andersson, David; Grundström, Christin; et al.
Nucleic Acids Research, Oxford University Press 2019, Vol. 47, (11) : 5712-5722
ter Beek, Josy; Parkash, Vimal; Bylund, Göran; et al.
Biophysical Journal, CELL PRESS 2019, Vol. 116, (3) : 485A-485A
Wolf-Watz, Magnus; Rogne, Per; Sauer-Eriksson, A. Elisabeth; et al.
Journal of Medicinal Chemistry, American Chemical Society (ACS) 2018, Vol. 61, (9) : 4165-4175
Kulén, Martina; Lindgren, Marie; Hansen, Sabine; et al.
Environmental Science and Technology, American Chemical Society (ACS) 2018, Vol. 52, (20) : 11865-11874
Zhang, Jin; Grundström, Christin; Brännström, Kristoffer; et al.
Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences 2017, Vol. 114, (24) : 6298-6303
Kovermann, Michael; Grundström, Christin; Sauer-Eriksson, A. Elisabeth; et al.
Cell chemical biology, Vol. 23, (3) : 404-414
Good, James A. D.; Andersson, Christopher; Hansen, Sabine; et al.
Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, (51) : 14733-14738
Hall, Michael; Grundström, Christin; Begum, Afshan; et al.
PLOS ONE, Public Library Science 2016, Vol. 11, (4)
Iakovleva, Irina; Begum, Afshan; Brännström, Kristoffer; et al.
PLOS ONE, Public Library Science 2016, Vol. 11, (4)
Nilsson, Lina; Larsson, Andreas; Begum, Afshan; et al.
Environmental Science and Technology, Vol. 50, (21) : 11984-11993
Zhang, Jin; Begum, Afshan; Brännström, Kristoffer; et al.
Plant Physiology, American Society of Plant Biologists 2015, Vol. 167, (3) : 950-962
Benlloch, Reyes; Shevela, Dmitriy; Hainzl, Tobias; et al.
Nature Communications, Vol. 6
Hainzl, Tobias; Sauer-Eriksson, A. Elisabeth
PLOS ONE, Public Library Science 2015, Vol. 10, (5)
Iakovleva, Irina; Begum, Afshan; Pokrzywa, Malgorzata; et al.
Journal of Medicinal Chemistry, Vol. 58, (16) : 6507-6515
Iakovleva, Irina; Brännström, Kristoffer; Nilsson, Lina; et al.
Nature Communications, Macmillan Publishers Ltd. 2015, Vol. 6
Kovermann, Michael; Ådén, Jörgen; Grundström, Christin; et al.
Protein Expression and Purification, Elsevier 2014, Vol. 96 : 39-47
Edwin, Aaron; Grundström, Christin; Wai, Sun Nyunt; et al.
Nature Structural & Molecular Biology, Nature Publishing Group 2014, Vol. 21, (1) : 49-56
Hogg, Matthew; Osterman, Pia; Bylund, Göran; et al.
FEBS Open Bio, Elsevier 2013, Vol. 3 : 263-270
Edwin, Aaron; Rompikuntal, Pramod; Björn, Erik; et al.
Advances in Yersinia Research, New York: Springer 2012 : 357-363
Eriksson, Jonas; Grundström, Christin; Sauer-Eriksson, A Elisabeth; et al.
Nucleic Acids Research, Vol. 40, (6) : 2611-2622
Hogg, Matthew; Sauer-Eriksson, A Elisabeth; Johansson, Erik
Protein Expression and Purification, Elsevier 2012, Vol. 86, (2) : 127-134
Paracuellos, Patricia; Öhman, Anders; Sauer-Eriksson, A Elisabeth; et al.
Nature Structural & Molecular Biology, Vol. 18, (3) : 389-391
Hainzl, Tobias; Huang, Shenghua; Meriläinen, Gitte; et al.
PLOS ONE, Vol. 6, (12) : e28458-
Huang, Shenghua; Hainzl, Tobias; Grundström, Christin; et al.
Acta Crystallographica. Section F: Structural Biology and Crystallization Communications, Vol. 66, (Pt 3) : 337-341
Wikström Hultdin, Ulrika; Lindberg, Stina; Grundström, Christin; et al.
The FEBS Journal, Wiley 2010, Vol. 277, (16) : 3368-3381
Wikström Hultdin, Ulrika; Lindberg, Stina; Grundström, Christin; et al.
The FEBS Journal, Wiley InterScience 2009, Vol. 276, (7) : 1999-2011
Lundberg, Erik; Olofsson, Anders; Westermark, Gunilla T; et al.
The FEBS Journal, Wiley InterScience 2009, Vol. 276, (15) : 4051-4060
Olofsson, Anders; Lindhagen Persson, Malin; Vestling, Monika; et al.
Analytical Biochemistry, Elsevier 2009, Vol. 385, (2) : 374-376
Olofsson, Anders; Sauer-Eriksson, A Elisabeth; Öhman, Anders
Recent advances in Transthyretin evolution, structure and biological functions, Springer Berlin/Heidelberg 2009 : 109-122
Sauer-Eriksson, Elisabeth; Linusson, Anna; Lundberg, Erik
Molecular and Cellular Endocrinology, Elsevier Ireland Ltd 2008, Vol. 295, (1-2) : 48-58
Morgado, Isabel; Melo, Eduardo P; Lundberg, Erik; et al.
Proc Natl Acad Sci U S A, Vol. 104, (38) : 14911-6
Hainzl, Tobias; Huang, Shenghua; Sauer-Eriksson, Elisabeth
Acta Crystallographica. Section F: Structural Biology and Crystallization Communications, Vol. 63, (Pt 8) : 695-700
Karlsson, Anders; Sauer-Eriksson, Elisabeth
Journal of Molecular Biology, Vol. 374, (1) : 186-94
Olofsson, Anders; Borowik, Tomasz; Gröbner, Gerhard; et al.
Biochem J, Vol. 404, (1) : 63-70
Olofsson, Anders; Lindhagen-Persson, Malin; Sauer-Eriksson, Elisabeth; et al.
J Struct Biol, Vol. 153, (1) : 85-96
Gariani, Talal; Samuelsson, Tore; Sauer-Eriksson, Elisabeth
Journal of Structural Biology, San Diego: Academic Press 2006, Vol. 155, (3) : 445-457
Lundberg, Erik; Bäckström, Stefan; Sauer, Uwe; et al.
Journal of Biological Chemistry, Vol. 281, (1) : 477-83
Olofsson, Anders; Sauer-Eriksson, Elisabeth; Öhman, Anders
RNA, Vol. 11, (7) : 1043-50
Hainzl, Tobias; Huang, Shenghua; Sauer-Eriksson, Elisabeth
Biochemistry, Vol. 44, (26) : 9290-9299
Hörnberg, Andreas; Wikström Hultdin, Ulrika; Olofsson, Anders; et al.
Biochemistry, Vol. 44, (39) : 13063-70
Karlsson, Anders; Olofsson, Anders; Eneqvist, Therese; et al.
Organic and biomolecular chemistry, London, U.K.: Royal Society of Chemistry 2005, Vol. 3, (15) : 2817-2823
Åberg, Veronica; Norman, Fredrik; Chorell, Erik; et al.
Journal of Biological Chemistry, Vol. 279, (25) : 26411-6
Eneqvist, Therese; Lundberg, Erik; Karlsson, Anders; et al.
Biochimica et Biophysica Acta, Amsterdam: Elsevier 2004, Vol. 1700, (1) : 93-104
Hörnberg, Andreas; Olofsson, Anders; Eneqvist, Therese; et al.
The FEBS Journal, John Wiley & Sons 2003, Vol. 270, (3) : 518-532
Eneqvist, Therese; Lundberg, Erik; Nilsson, Lars; et al.
Curr Opin Struct Biol, Vol. 13, (1) : 64-70
Sauer-Eriksson, Elisabeth; Hainzl, Tobias

Research groups

Head of research
Elisabeth Sauer-Eriksson Lab