NMR structure of the cyclin-dependent kinase inhibitor Sic1 with the ubiquitin ligase Cdc4 (grey). Out of the nine phosphorylation sites of Sic 1 (spheres) the contacts with T45 and S76 are shown (orange and blue).The fuzzy linker region (shown by dotted line) of the Ultrabithorax transcription factor (orange) connects the homedomain with the Extradenticle homedomain (blue) (PDB code 1bi). Alternative splicing modulates the length of the fuzzy region and thus its DNA (grey) binding affinity. Other regulatory fuzzy regions of Ultrabithorax are also shown by dotted lines.
Fuzzy complexes are protein complexes, where structural ambiguity or multiplicity exists and is required for biological function.[1][2] Alteration, truncation or removal of conformationally ambiguous regions impacts the activity of the corresponding complex.[3][4][5] Fuzzy complexes are generally formed by intrinsically disordered proteins.[6][7] Structural multiplicity usually underlies functional multiplicity of protein complexes [8][9][10] following a fuzzy logic. Distinct binding modes of the nucleosome are also regarded as a special case of fuzziness.[11][12]
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^Bhattacharyya, R. P; Reményi, Attila; Good, Matthew C; Bashor, Caleb J; Falick, Arnold M; Lim, Wendell A (2006). "The Ste5 Scaffold Allosterically Modulates Signaling Output of the Yeast Mating Pathway". Science. 311 (5762): 822–6. Bibcode:2006Sci...311..822B. doi:10.1126/science.1120941. PMID 16424299. S2CID 13882487.
^Liu, Ying; Matthews, Kathleen S; Bondos, Sarah E (2009). "Internal Regulatory Interactions Determine DNA Binding Specificity by a Hox Transcription Factor". Journal of Molecular Biology. 390 (4): 760–74. doi:10.1016/j.jmb.2009.05.059. PMC 2739810. PMID 19481089.
^Romero, P; Obradovic, Z; Kissinger, C. R; Villafranca, J. E; Garner, E; Guilliot, S; Dunker, A. K (1998). "Thousands of proteins likely to have long disordered regions". Pacific Symposium on Biocomputing: 437–48. PMID 9697202.
^Wright, Peter E; Dyson, H. Jane (1999). "Intrinsically unstructured proteins: Re-assessing the protein structure-function paradigm". Journal of Molecular Biology. 293 (2): 321–31. doi:10.1006/jmbi.1999.3110. PMID 10550212.
^Galea, Charles A; Nourse, Amanda; Wang, Yuefeng; Sivakolundu, Sivashankar G; Heller, William T; Kriwacki, Richard W (2008). "Role of Intrinsic Flexibility in Signal Transduction Mediated by the Cell Cycle Regulator, p27Kip1". Journal of Molecular Biology. 376 (3): 827–38. doi:10.1016/j.jmb.2007.12.016. PMC 2350195. PMID 18177895.
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^Tsui, K; Dubuis, S; Gebbia, M; Morse, R. H; Barkai, N; Tirosh, I; Nislow, C (2011). "Evolution of Nucleosome Occupancy: Conservation of Global Properties and Divergence of Gene-Specific Patterns". Molecular and Cellular Biology. 31 (21): 4348–55. doi:10.1128/MCB.05276-11. PMC 3209338. PMID 21896781.
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