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Research in Nalle Jonsson's group

Chaperone function
(Laila Villebeck)

An intensely debated question is whether the chaperone class known as the chaperonins  unfold proteins actively, by a mechanism that we may call ”protein massage”, or if they merely act as passive isolation chambers. We approach this issue by investigating molecular details in the interaction between the eukaryotic chaperonin TRiC (also known as CCT) and its natural substrate actin. Rearrangements in the actin molecule upon interaction with the chaperone are characterized by determining changes in distance between fluorescent probes in the actin molecule using FRET-measurements.

The protein folding disease ALS
(Anna Katrine Museth)

The fatal neurodegenerative disease ALS (Amyotrophic Lateral Sclerosis) is strongly coupled to misfolding and aggregation of the protein superoxide dismutase (SOD). To find the molecular basis for ALS we perform a detailed characterization of the structural and dynamical properties of a set of SOD-protein variants with different ALS-associated mutations in the CuZnSOD-gene. We use hydrogen/deuterium exchange experiments, which are monitored by NMR and mass spectrometry, to measure interactions and the conformational dynamics in the ALS-associated protein variants.

Protein adsorption on solid surfaces
(Martin Lundqvist)

Knowledge about structure and dynamics of surface-adsorbed proteins is important in the development of devices that interact with biological systems. We investigate details of the conformational rearrangements that occur upon protein adsorption to solid surfaces. The use of solid nanoparticles with 5-15 nm diameters allows us to use standard spectroscopic methods for measurements. We also use de novo peptide design for construction of nanoparticle-peptide complexes with well-defined structure and biological function.

Enzyme mechanisms
(Gunnar Höst)

There is an increasing need for catalysts with high specificity in the modern biotech industry, and for that reason we develop enzymes with novel catalytic activities and reaction specificities, using rational design guided by automated docking methods, combined with library screening. The well-studied enzyme carbonic anhydrase is used as a scaffold upon which new functionalities are introduced by genetic engineering methods.

In one project, we introduce an engineered catalytic machinery in carbonic anhydrase, while utilizing the preexisting natural active site exclusively for substrate binding. By inserting catalytically active histidine residues in strategically chosen positions, we have achieved hydrolysis of a designed ester substrate.

In another project, we engineer the specificity of the natural active site of carbonic anhydrase. The physiological reaction catalyzed by carbonic anhydrase is the conversion of carbon dioxide into bicarbonate. However, the active site is also capable of catalyzing the hydrolysis of certain small ester substrates. We have achieved a greatly increased specificity for ester substrates with long acyl chains by engineering mutants with a larger substrate binding cavity. In an extension of this project, we are constructing mutants with increased activity for even larger substrates, that can be of medical or industrial interest. 

Responsible for this page: Gunnar Höst

Last updated: 01/16/07