Speaker: Monika Fuxreiter, PhD. MTA-DE Laboratory of Protein Dynamics, Biochemistry and Molecular Biology, University of Debrecen (Hungary)
Organizer: IRB Barcelona
Date: Wednesday, February 28, 9:30h
Place: Aula Fèlix Serratosa, Parc Científic de Barcelona, Spain
Host: Miquel Pons (UB) and Xavier Salvatella (IRB Barcelona)
The proposal that coupled folding to binding is not an obligatory mechanism for intrinsically disordered proteins was put forward 10 years ago. The notion of fuzziness implies that conformational heterogeneity can be maintained upon interactions of proteins, which has a functional impact either on regulated assembly or activity of the corresponding complexes. In the past decade increasing experimental data provided insights into the mechanisms, pathways and regulatory modes. The effects of structural diversity and transient contacts on protein assemblies have been collected and systematically analyzed (FuzDB, http://protdyn-database.org). Fuzziness has also been exploited to understand higher-order protein organizations, including non-membrane-bound compartments. All these advances enabled the assessment of conformational heterogeneity in protein assemblies. Quantification of fuzziness informs on dynamical adaptations of proteins and provides a framework for stochastic structure-function relationships.
Wu, H, Fuxreiter M (2016) The Structure and Dynamics of Higher-Order Assemblies: Amyloids, Signalosomes, and Granules. Cell 165, 1055-1066.
M. Miskei, Cs. Antal, M. Fuxreiter (2017) FuzDB: database of fuzzy complexes, a tool to develop stochastic structure-function relationships for protein complexes and higher-order assemblies. Nucleic Acids Res. 45, D228-235.
M. Miskei et. al. (2017) Fuzziness enables context-dependence of protein interactions. FEBS Lett. 591, 2682-2695
M Fuxreiter (2012) Fuzziness: linking regulation to protein dynamics. Mol Biosystems 8, 168-177.
P. Tompa, M Fuxreiter (2008) Fuzzy complexes: polymorphism and structural disorder in protein–protein interactions. Trends in Biochem. Sci 33, 2-8
SCB and Chemistry and Molecular Pharmacology Programmes joint seminar