Structural Molecular Biology

Last changed: 12 December 2023

MD simulation of a fungal LPMO enzyme working on the surface of cellulose (Wu et al, 2013, J Biol Chem 288, 12828).

The teams led by Mats Sandgren, Jerry Ståhlberg, Gustav Nestor and Sabine Samples study molecular structure, function and biotechnical applications of biological macromolecules (proteins, carbohydrates, lipids), using X-ray crystallography, Cryo-EM, NMR spectroscopy, supercritical CO2 extraction, FTIR spectroscopy and other techniques.

Structural Molecular Biology team, 3 Oct 2023. From the left: Nils Mikkelsen (insert), Mats Sandgren, Mikolaj Chmielarz, Naike Schwenner, Piera Wiesinger, Topi Haataja, Gustav Nestor, Laura Okmane, Jerry Ståhlberg, Andreia Massamby, Sabine Samples (insert)

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Structural Molecular Biology & Food Biotechnology, 12 Oct 2022. From the left: Naike Schwenner, Mikolaj Chmielarz, Mats Sandgren, Volkmar Passoth, Nils Mikkelsen, Sabine Samples, Gustav Nestor, Giselle Martin Hernandez, Jerry Ståhlberg, Yashaswini Nagavara Nagaraj, Topi Haataja, Piera Wiesinger, Laura Okmane

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Structures “R” Us – We can determine the positions of the atoms in protein molecules by X-ray crystallography. Protein molecules may pack into crystals in certain conditions. Intense X-ray radiation of crystals gives a diffraction pattern from which an electron density map can be calculated. In the map we can build a 3D model of the protein structure.

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NMR spectroscopy – The 1H NMR spectra to the left, of glucomannan after degradation with different GH45 enzymes, show differences in the degradation pathways. [Okmane et al., 2022, Carbohydr. Polym. 277, 118771].

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NMR spectroscopy – The orientation of a sugar hydroxyl proton in a lectin/mannoside complex, determined from intra- and intermolecular NOEs. [Nestor et al., 2021, Glycobiology, 31, 508-518].

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Functionalized protein nanofibers – Small carrier proteins, e.g. Sup35, that spontaneously aggregate to nanofibrils, were fused with functional proteins, and mixed with unmodified carrier proteins to produce nanofibrils for biotechnical applications [Schmuck, B, 2018, Acta Univ Agric Sueciae 2018:57, Doctoral thesis; Schmuck et al., 2017, Biotechnol J 12, 1600672; Schmuck et al., 2018, PLOS One 13, e0196250; Schmuck et al., 2018, ACS Nano 12, 9363-71; Schmuck et al., 2019, J Biol Chem 294, 14966-77].

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Functionalized protein nanofibers – Extracellular recombinant expression of antibody-binding Sup35-ZZ chimeric protein in the methylotrophic yeast Komagataella pastoris proved to be a highly successful strategy. The separation of the fibril material from cells requires only centrifugation and resuspension in saline water [Schmuck et al., 2018, ACS Nano 12, 9363-71]. Hopefully even higher yields can be otained by using efficient filamentous fungal expression hosts such as Trichoderma reesei.

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We study structure and function of key biomass-degrading enzymes to find out how to best harness Nature’s own tools for environmentally friendly utilisation of biomass from agriculture and forestry.

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Video Gallery

MD simulation of a fungal LPMO enzyme working on the surface of cellulose (Wu et al, 2013, J Biol Chem 288, 12828).

Exploring Protein Structure: Synchrotron X-ray Crystallography Insights.

About Us

Mats Sandgren and Jerry Ståhlberg have >30 years track record of publications in high-impact journals, including JACS, PNAS, JMB and JBC, on structure-function of key enzymes from fungi and bacteria that degrade cellulose and other polysaccharides. The results have paved the way for improved enzymes and industrial processes through enzyme engineering and genome mining.

Gustav Nestor’s research is focused on NMR method development and NMR studies on carbohydrates, carbohydrate-binding proteins and carbohydrate-active enzymes. He is involved in several collaborative projects using NMR spectroscopy on biomolecules.

Sabine Sampels is expert on lipids, oxidation and antioxidants, with main focus on the quality of fish, meat and products thereof through the whole food chain. Sustainable production of food with high nutritional value is an overarching research goal.

Our groups are strategically located at SLU Biocenter in Uppsala, a modern research center covering the entire scale from fundamental to applied research, in collaborative initiatives within the areas of biomolecules, microorganisms, plants and food, with a common mission:
“Science and Education for Sustainable Life”.

Research

An important area is fundamental research of structure and function of proteins, both within and outside cells, including isolation or recombinant expression, purification and structural determination of biological catalysts, enzymes, and characterization of their function in biosynthesis and biodegradation in nature.

Structure determination with X-ray crystallography is a core competence and we have deposited over 100 structures at the Protein Data Bank (PDB). Recently we have also started to expand into Cryo-EM and more NMR for macromolecular structure studies.

One major theme is basic and applied research of biological reaction systems, enzymatic and microbial, for biotechnical applications for conversion of biomass, e.g. from agriculture and forestry, for production of renewable fuels, chemicals, materials, food and feed components, to increase usability of renewable plant biomass and thereby contribute to reduction of fossil resource usage and reduced greenhouse gas emissions.

We also collaborate closely with the Food Biotechnology unit, lead by Professor Volkmar Passoth, in the LipoDrive program, to exploit oil-accumulating yeasts for conversion of carbohydrates from plant biomass to lipids, for production of e.g. biodiesel and fish feed.