Fuzzy complex

[1][2] Alteration, truncation or removal of conformationally ambiguous regions impacts the activity of the corresponding complex.

The most pertinent example is the cyclin-dependent kinase inhibitor Sic1, which binds to the SCF subunit of Cdc4 in a phosphorylation dependent manner.

[16] Clamp,[17] flanking [18][19] and random complexes[20][21] are dynamic, where ambiguous conformations interchange with each other and cannot be resolved.

[24] Fuzzy regions modulate the conformational equilibrium [25] or flexibility [3][26] of the binding interface via transient interactions.

Alternative splicing can modulate the length of fuzzy regions resulting in context-dependent binding (e.g. tissue-specificity) on the complex.

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 homeodomain with the Extradenticle homeodomain (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.