Health Research DATABASE

FuzDB: Health Research DATABASE


Health Research DATABASE
Fuzzy complexes are specific protein assemblies, where structural ambiguity or multiplicity exists and is also required for biological function. Two criteria have to be fulfilled to define a fuzzy protein complex:

1, Structural evidence indicating that a protein region does not have a well-defined structure in complex with a partner. An intrinsically disordered region may alternatively fold into ensembles of structured conformations or remain largely disordered, exhibiting fast exchange of conformations even in the complex state. Fuzzy regions usually do not appear in crystal structures and by most spectroscopic methods their spectrum in the bound state is highly similar to that in the unbound state.

2, Biochemical evidence demonstrating that manipulation of conformationally heterogeneous regions impacts the biological activity of the complex.  For example alteration, truncation or removal of the fuzzy region modulates binding affinity, specificity, transcriptional activity, enzymatic parameters or localization. Truncation of fuzzy regions usually changes activity in gradual manner.

Fuzzy regions are often targeted by post-translational modifications to fine-tune activity of the complex. Depending on the cellular context or physiological conditions, fuzzy regions can adopt different forms and perform different functions. Higher-order assemblies, such as amyloids, signalosomes or cellular granules can also be considered as fuzzy structures.

This database collects experimentally verified fuzzy complexes. Our motivation is to facilitate the identification of further examples and to gain insights into the mechanisms of their functioning.


Citation for the database:
Sharma R, Raduly Z, Miskei M, Fuxreiter M (2015) Fuzzy complexes: Specific binding without complete folding. FEBS Letters 589, 2533-42 abstract

Further references:
P. Tompa and M Fuxreiter (2008) Fuzzy complexes: polymorphism and structural disorder in protein–protein interactions. Trends in Biochem.Sci 33, 2-8 abstract
M Fuxreiter (2012) Fuzziness: linking regulation to protein dynamics. Mol Biosystems 8, 168-177 abstract
M.Fuxreiter, I. Simon, S. Bondos (2011) Dynamic protein-DNA recognition: beyond what can be seen. Trends in Biochem Sci 36, 415-423. abstract
Monika Fuxreiter and Peter Tompa (Eds) Fuzziness: Structural disorder in protein complexes, Landes Bioscience/Springer, Austin, NY 2011 abstract1, 2
M Fuxreiter, P Tompa, I Simon, VN Uversky, JC Hansen, F Asturias (2008) Malleable machines take shape in eukaryotic transcription regulation.
Nat Chem Biol 4, 728-737 abstract

If you have any questions, please contact Monika Fuxreiter ().







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