What are intrinsically disordered proteins and their functions?

Intrinsically disordered proteins (IDPs) or regions (IDRs) lack stable 3D structure under physiological conditions, existing as dynamic ensembles of conformations. IDPs are enriched in charged and polar residues, depleted in hydrophobic residues. Functions enabled by disorder: promiscuous binding to multiple partners (hub proteins in signaling), fast association/dissociation kinetics, large binding surfaces relative to size, and post-translational modification sites. Examples include p53 transactivation domain, CREB binding domain, and tau protein. Disorder-to-order transitions often occur upon binding (coupled folding-binding). IDPs are prevalent in signaling, transcription, and regulation. They are associated with aggregation diseases when misregulated and present challenges for traditional structural biology.