Pernilla Wittung-Stafshede's Protein Folding Lab

We use biophysical methods to study (1) the role of cell-like conditions on protein chemistry and (2) copper-transport mechanisms in human cells.

The question of how a protein is formed is one of life's great mysteries.The understanding of protein folding and misfolding processes, and how external factors affect these reactions, are critical for finding rational treatment of many debilitating conditions like Alzheimer´s and Parkinson's disease, type II diabetes, prion diseases, and Menke's and Wilson's diseases. Knowledge about protein folding is also crucial in protein design and protein-structure prediction efforts. The projects in my lab focus on fundamental aspects of protein folding reactions using model systems (mechanistic path) as well as on specific human proteins involved in key metabolic pathways (medical path).

Some of my research aims to increase our fundamental knowledge of how proteins fold in vitro and in vivo. The major focus of this part is on two key classes of proteins: cofactor-binding proteins and oligomeric proteins. Folding of these proteins does not only involve polypeptide folding, but also inter-protein interactions. Folding pathways for these proteins may be affected by cofactor interactions and protein-protein interactions, respectively. Previous and/or ongoing/future projects focus on azurin (copper), flavodoxin (flavin), myoglobin (heme), co-chaperonin proteins (heptamers), and VlsE (dimer). To mimic the crowded cellular environment in vivo, experiments are performed in the presence of crowding agents.
Another branch of my research aims to understand the biophysical behavior of proteins involved in human cellular copper transport. Copper is an essential metal in many enzymes that is required from the diet. Since free copper ions are toxic, copper is specifically transported by proteins. Inside cells, copper chaperones deliver copper to Wilson and Menkes proteins in the Golgi network, which then load the metal onto targets, such as ceruloplasmin which is a plasma protein important for iron metabolism. Ongoing and future projects within this scope concerns the folding, binding and transfer properties of human and bacterial copper chaperones, different domains of the human Wilson protein as well as ceruloplasmin.

For all projects, a range of biophysical and biochemical techniques are combined with strategic protein mutagenesis and theoretical approaches to characterize the folding reactions of selected target proteins.

WE HAVE OPENINGS FOR EXCELLENT STUDENTS THAT WANT TO BECOME
POSTDOCS. IF YOU ARE INTERESTED, CONTACT ME!

Instrumentation
Chirascan stopped-flow mixer (with CD, fluorescence and absorption detection)
Fluorometer
ITC and DSC micro-calorimeters
Circular dichroism spectropolarimeter
two AKTA purifiers
polarimeter

Lab members
Maria Espling
Alexander Christensen
Moritz Muller
Ximena Aguilar
Istvan Horvath
Jörgen Åden
Christoph Weise


Contact Information

Pernilla Wittung-Stafshede
Professor, Chemistry Department
Umeå University
901 87 Umeå, Sweden
pernilla.wittung@chem.umu.se
office phone: +46-90-786 5347
lab phone: +46-90-786 5268

Publications

Author

Title

Year sorteringsordning

Fulltext

Palm-Espling, Maria
Lundin, Christina
Björn, Erik; et al.

Interaction between anticancer drug Cisplatin and copper chaperone Atox1 in human melanoma cells
Protein peptide letters, 21(1): 63-68

2014

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Christiansen, Alexander
Wittung-Stafshede, Pernilla

Synthetic crowding agent dextran causes excluded volume interactions exclusively to tracer protein apoazurin
FEBS Letters, 588(5): 811-814

2014

-

Palm-Espling, Maria
Andersson, David C.
Björn, Erik; et al.

Determinants for simultaneous binding of copper and platinum to human chaperone Atox1: Hitchhiking not hijacking
PLoS ONE, 8(7): e70473-

2013

Download

Christiansen, Alexander
Wittung-Stafshede, Pernilla

Quantification of excluded volume effects on the folding landscape of Pseudomonas aeruginosa Apoazurin In Vitro
Biophysical Journal, 105(7): 1689-1699

2013

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Wittung-Stafshede, Pernilla

In Vitro effects of Macromolecular Crowding on Protein Stability, Structure and Folding
Biophysical Journal, 104(2): 576A-576A

2013

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Horvath, Istvan
Sellstedt, Magnus
Weise, Christoph; et al.

Modulation of α-synuclein fibrillization by ring-fused 2-pyridones: Templation and inhibition involve oligomers with different structure
Archives of Biochemistry and Biophysics, 532(2): 84-90

2013

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Andersson, Emma K.
Bengtsson, Christoffer
Evans, Margery L.; et al.

Modulation of Curli Assembly and Pellicle Biofilm Formation by Chemical and Protein Chaperones
Chemistry and Biology, 20(10): 1245-1254

2013

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Wittung-Stafshede, Pernilla

Effects of macromolecular crowding on protein folding in vitro
Abstract of Papers of the American Chemical Society, 245

2013

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Mikaelsson, Therese
Ådén, Jörgen
Johansson, Lennart B-Å; et al.

Direct Observation of Protein Unfolded State Compaction in the Presence of Macromolecular Crowding
Biophysical Journal, 104(3): 694-704

2013

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Nilsson, Lina
Ådén, Jörgen
Niemiec, Moritz S; et al.

Small pH and Salt Variations Radically Alter the Thermal Stability of Metal-Binding Domains in the Copper Transporter, Wilson Disease Protein
Journal of Physical Chemistry B, 117(42): 13038-13050

2013

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Page Editor: Pernilla Wittung-Stafshede
2012-01-12

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