Database of fuzzy protein complexes|
Citation: Nucleic Acids Research (2017) Jan 4;45(D1):D228-D235. abstract full [PDF]
FuzPred: Prediction of fuzzy protein interactions is available!
The new FuzDrop site with Alphafold predictions is now available
Conformational diversity of any kind, either static or dynamic, which has an impact on the regulated formation and function of protein complexes or higher-order assemblies is termed as fuzziness. In the case of static polymorphism, alternative conformations of the same interacting elements are stabilized within the assembly. In the case of dynamic disorder, the intrinsically disordered region (IDR) retains conformational freedom within the assembly.
Fuzzy regions are utilized to fine-tune properties of protein complexes according to the cellular context and physiological conditions. Higher-order assemblies, such as amyloids, signalosomes and cellular granules also exhibit structural polymorphism or dynamic disorder as a key to their function. The evolution of the concept is overviewed here.
This database assembles fuzzy protein complexes based on experimental evidence.
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 changes affecting structurally heterogeneous regions impact the formation, function or regulation of the complex. Alteration, truncation or removal of the fuzzy region could modulate binding affinity, specificity, transcriptional activity, enzymatic parameters or localization. Truncation of fuzzy regions is often accompanied by gradual changes in biological activity.
Our motivation is to collect experimental data facilitating the identification and analysis of fuzzy complexes as well as to provide insights into the mechanisms of their functioning.
Marton Miskei, Csaba Antal and Monika Fuxreiter (2017) FuzDB: database of fuzzy complexes, a tool to develop stochastic structure-function relationships for protein complexes and higher-order assemblies. Nucleic Acids Research 45(D1):D228-D235. abstract full [PDF]
P. Tompa and M Fuxreiter (2008) Fuzzy complexes: polymorphism and structural disorder in protein–protein interactions. Trends in Biochem.Sci 33,
H. Wu and M Fuxreiter (2016) The Structure and Dynamics of Higher-Order Assemblies: Amyloids, Signalosomes, and Granules. Cell. 165(5):1055-1066. abstract
M Fuxreiter (2018) Fuzziness in protein interactions - a historical perspective. J Mol Biol. doi: 10.1016/j.jmb.2018.02.015. 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
Sharma R, Raduly Z, Miskei M, Fuxreiter M (2015) Fuzzy complexes: Specific binding without complete folding. FEBS Letters 589, 2533-42 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 (firstname.lastname@example.org).
FuzDB v3.3 (2016.10.12.)
Text download for search results was added.
FuzDB v3.2 (2016.08.01.)
Topology and mechanism filters were included in the advanced search.
FuzDB v3.1 (2016.07.20.)
The Upload module was reshaped, additional safety filter was added.
FuzDB v3.0 (2016.06.22.)
Classes and FAQs were added to the menu. Home was redesigned.
FuzDB v2.0 (2016.01.30.)
17 complexes were added, including higher-order assemblies.
FuzDB v1.0 (2015.06.19.)
Release of the database with 85 complexes
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