Exjobbsförslag från företag

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Förslaget inkom 2009-12-29

Structural biochemistry/biophysics: PP2A as regulator of intracellular protein phosphorylation

Dynamic phosphorylation and dephosphorylation of proteins are fundamental mechanisms for cell regulation. More than 30 percent of intracellular human proteins are believed to be reversibly phosphorylated and many human diseases can be attributed to a malfunctioning of kinases and phosphatases.
Protein Phosphatase (PP) 2A is one of the major protein serine/threonine phosphatases responsible for regulating the levels of intracellular protein phosphorylation. Together with PP1 it accounts for more than 90 % of all Ser/ Thr phosphatise activities in most tissues and cells. The enzyme is involved in the control of a wide range of cellular processes, including DNA replication, transcription, cell cycle progression, RNA splicing, development, and apoptosis. Its capacity to regulate these processes is governed by regulatory and targeting subunits as well as posttranslational modifications.
PP2A is composed of a core dimer, formed by the catalytic subunit (PP2A-C) and a scaffolding subunit (PP2A-A) that complexes with one of the several regulatory subunits (PP2A-B). Recent structural data on the core dimer and the holoenzyme complex led to fundamental advances in understanding this sytem.
PP2A is also regulated by the action of PTPA (PP2A phosphatase activator). This protein is highly conserved from humans to yeast and forms a stable complex with the PP2A core dimer. However, the mechanistic and functional role of PTPA remains to be elucidated.
The aim of this project is to characterize PTPA and the interaction with the components of the PP2A complex using biophysical methods. The single proteins will be recombinantely expressed and purified to homogeneity. Interactions studies encompass fluorescence and CD spectroscopy, ITC and gelfiltration. Furthermore PTPA-PP2A complexes will be crystallized to obtain high resolution information on this system.

You will work in a highly motivated team and well-equipped laboratory at the Karolinska Institutet, Department of Medical Biochemistry and Biophysics, Unit for Biophysics (Head: Professor Pär Nordlund).
The start date for this project is as soon as possible (master thesis or project work).

If you think the project is interesting, please send a short letter about yourself and your motivation to work in the protein biochemistry field to Christian Löw ([email protected]).


Informationen om uppsatsförslag är hämtad från Nationella Exjobb-poolen.