Protein disorder/structure and amphitropism
Protein disorder/structure and amphitropism are important in many phenomena that are under intensive scrutiny. These phenomena include:
i) Interactions between proteins and lipid membranes and how this is regulated is important for cytoskeleton motility, sustaining a high level of membrane organization, and in understanding the action of toxic protein multimers that again are interesting from a medical perspective.
ii) Protein folding and misfolding. This is an intrinsically interesting problem, but also one of high relevance for medical research. Many diseases have links to misfolding behaviour, such as Alzheimers, prionic diseases and other afflictions.
iii) Cellular signalling. Protein flexibility and dynamics are central to cellular signalling and especially for the one-to-many protein interactions that have been found to be particularly relevant for higher eukaryotic life.
Amphitropism, proteins and the lipid membrane
A large part of the highly organized and compartmentalized eukaryotic cell genomes code for proteins that are dynamic, disordered and flexible yet still functional. Many of these are involved in regulated and/or transient interaction with lipid membranes in the cell, such as the outer cell membrane, nucleus membrane, mitochondria and other organelles. Such systems – based on protein amphitropism – are very important to life, but knowledge lags behind what we know of the soluble, ordered proteins. The fundamental goal of the research group is thus to understand how protein-membrane interaction and protein disorder in general is used in the functional requirements of the cell, to understand what can go wrong, and whether these mechanisms can be exploited, e.g. in the development of new classes of drugs. We use liquid-state NMR, fluorescence and circular dichroism in combination with different model lipid membranes to explore such systems. We also work with surface Plasmon resonance and other biophysical techniques, as well as cultured cells for testing the effect of new constructs on these.