Intrinsically unstructured proteins

• Disordered proteins exhibit order at the level of primary and secondary/tertiary structure that correlates with their specific functions (pg 527)

• Disordered proteins do not perform enzymatic activity: requires a rigid fold (pg 527)

• Functions of disordered proteins linked to their structural disordered and can be classified into 28 categories (pg 527)

• Five broad functional classes (pg 527):
  • Entropic chains
  • Effectors like inhibitors -- modify the activity of a single parter protein or assembled proteins
  • Scavengers -- store and/or neutralize small ligands
  • Assemblers -- assemble, stabalize, and regulate large multiprotein complexes like the ribosome
  • Molecular recognition like display sites that mediates regulatory postranslational modification like phosphorylation (pg 528)

• Disordered proteins in above functional classes involved in regulation of key cellular processes, such as transcription, translation, signal transduction, and the cell cycle (pg 528)

• The functions of disordered proteins depends on their disordered state (pg 529)
• The disorder-order transition, where the protein folds when binding to its target, causes a large decrease in conformational entropy that allows binding strength to be uncoupled from specificity, making highly specific interactions reversible (pg 529)
• The open structure of the disordered protein is preserved when they complex with their target and provides a disproportionately large binding surface and multiple contact points (pg 530)
• Disordered proteins can adopt different structures upon different stimuli or with different partners (pg 530)
• Another advantage -- increased speed of interaction (pg 530)

• Compared with average folded protein in PDB, disordered proteins (pg 531):
  • enriched in P, E, K, S, and Q
  • depleted in W, Y, F, C, I, L, and N

• Disordered proteins display residual structure and fall into two structural classes: coil-like or premolten-globule-like (pg 532)

• Conformation disordered proteins adopt largely defined by their interacting partner more than their amino acid sequences (pg 532)