Mikael Oliveberg

Research program
Protein Folding, Misfolding and Neurodegenerative Disease: How proteins maintain their right shapes and what happens when they don’t.

Address:
e-mail: mikael.oliveberg@dbb.su.se
Phone: (+46)-8-16 2459
Fax: (+46)-8-15 3679
Home page: http://w3.dbb.su.se/~oliveberg/

Group members
Ellinor Haglund, Linda Hedberg, Andreas Hörnberg (working at Umeå University), Magnus Lindberg, Anna Nordlund

Project description
Proteins control our lives down to the smallest detail. Even so, the question of how a protein is formed is one of life’s great mysteries. In a split second, the floppy protein chain forms itself into a ball with a unique shape and function. Occasionally, however, they get trapped in a wrong shape and run amok with devastating consequences for the cells. The understanding of these protein folding and misfolding processes are critical for finding rational treatment of many debilitating conditions like Alzheimer’s disease, ALS and the prion diseases. Basically, the underlying principle is simple: the tension between fat and water. Just as fat is attracted to fat, and water to water, the proteins are controlled in the cells and join together correctly to form the right shape all by themselves. If one part loosens, it is automatically pulled back. This remarkable ability to self assemble is at least partly orchestrated by amino acids that sit like guards making sure that no wrong knots are made. If you remove them, the proteins distort, stick together by exposure of their greasy interior and kill the cells. Suddenly, the uniting force has been turned against us. But the most fascinating thing about proteins is not that they can go wrong, but that they function at all. What stops chaos from taking over?

Selected publications

“Systematically perturbed folding patterns of amyotrophic lateral sclerosis (ALS)-associated SOD1 mutants”
Mikael J. Lindberg, Roberth Byström, Peter M. Andersen and Mikael Oliveberg
(2005) Proc. Natl. Acad. Sci. USA. 102, 9754-9759.

“Folding of human apoSOD: disulphide reduction prevents dimerisation and produces marginally stable monomers”
Mikael J. Lindberg, Johanna Normark, Arne Holmgren and Mikael Oliveberg
(2004) Proc. Natl. Acad. Sci. USA. 101, 15893-15898.

“Scattered Hammond plots reveal second level of site-specific information in protein folding: phi' (beta‡)”
Linda Hedberg and Mikael Oliveberg
(2004) Proc. Natl. Acad. Sci. USA. 101, 7606-7611.

"Complete change of the protein folding transition state upon circular permutation"
Magnus O. Lindberg, Jeanette Tångrot and Mikael Oliveberg
(2002) Nature Struct Biol. 9, 818-822.

"Characterisation of the transition states for protein folding: 
Protein engineering analysis towards a new level of mechanistic detail"
Mikael Oliveberg
(2001) Current opinion in Structural Biology, 11:1, 94-100.

"Designed protein tetramer zipped together with a hydrophobic Alzheimer homology: a structural clue to amyloid assembly"
Daniel E. Otzen, Ole Kristensen and Mikael Oliveberg
(2000) Proc. Natl. Acad. Sci. USA., 97, 9907-9912.

Acknowledgements
Our research is funded by the Swedish Research Council, the Göran Gustafssons Research Foundation and Bertil Hållstens Research Foundation.

MIKAEL OLIVEBERG
Department of Biochemistry and Biophysics
Arrhenius Laboratories for Natural Sciences
Stockholm University
106 91 Stockholm, Sweden
Tel: + 46 8 162459 Fax: + 46 8 153679
mikael.oliveberg@dbb.su.se