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

Öhrvik, Helena
Wittung-Stafshede, Pernilla

Identification of New Potential Interaction Partners for Human Cytoplasmic Copper Chaperone Atox1: Roles in Gene Regulation?
International Journal of Molecular Sciences, 16(8): 16728-16739

2015

-

Perdersen, Martin Nors
Fodera, Vito
Horvath, Istvan; et al.

Direct Correlation Between Ligand-Induced alpha-Synuclein Oligomers and Amyloid-like Fibril Growth
Scientific Reports, 5

2015

Download

Chorell, Erik
Andersson, Emma
Evans, Margery L.; et al.

Bacterial Chaperones CsgE and CsgC Differentially Modulate Human α-Synuclein Amyloid Formation via Transient Contacts
PLoS ONE, 10(10): 1-11

2015

Download

Sharma, Sandeep K.
Chorell, Erik
Wittung-Stafshede, Pernilla

Insulin-degrading enzyme is activated by the C-terminus of alpha-synuclein
Biochemical and Biophysical Research Communications - BBRC, 466(2): 192-195

2015

-

Sharma, Sandeep K
Chorell, Erik
Steneberg, Pär; et al.

Insulin-degrading enzyme prevents alpha-synuclein fibril formation in a nonproteolytical manner
Scientific Reports, 5

2015

Download

Wittung-Stafshede, Pernilla

Tuning of Alpha-Synuclein Aggregation by Small Molecules and Bacterial Proteins
Biophysical Journal, 108(2): 522A-522A

2015

-

Singh, Pardeep
Chorell, Erik
Krishnan, K Syam; et al.

Synthesis of multiring fused 2‑pyridones via a nitrene insertion reaction: fluorescent modulators of α‑synuclein amyloid formation
Organic Letters, 17(24): 6194-6197

2015

-

Wittung-Stafshede, Pernilla

Unresolved questions in human copper pump mechanisms
Quarterly reviews of biophysics (Print), 48(4): 471-478

2015

Download

Evans, Margery L.
Chorell, Erik
Taylor, Jonathan D.; et al.

The Bacterial Curli System Possesses a Potent and Selective Inhibitor of Amyloid Formation
Molecular Cell, 57(3): 445-455

2015

-

Petzoldt, Svenja
Kahra, Dana
Kovermann, Michael; et al.

Human cytoplasmic copper chaperones Atox1 and CCS exchange copper ions in vitro
Biometals, 28(3): 577-585

2015

-


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

Print page