Why do IDPs & IDRs lack structure? Lack a ligand or partner? Denatured during isolation? Folding requires conditions found inside cells? Lack of folding encoded by amino acid sequence? Solution IDPs (Intrinsically disordered protein) and IDRs (Intrinsically disordered regions) lack structure due to lack of folding encoded by amino acid seuence. In general, IDPs are characterized by a low content of bulky hydrophobic amino acids and a high proportion of polar and charged amino acids, usually referred to as low hydrophobicity. This property leads to good interactions with water. Furthermore, high net charges promote disorder because of electrostatic repulsion resulting from equally charged residues. Thus disordered sequences cannot sufficiently bury a hydrophobic core to fold into stable globular proteins. Some proteins are fully disordered while some are partial. Partial disordered proteins have some disordered regions (IDRs). Hence, IDPs and IDRs have no fix structure and cover a spectrum of states from fully unstructured to partially structured and include random coils, (pre-)molten globules, and large multi-domain proteins connected by flexible linkers..

1. Why do IDPs & IDRs lack structure? Lack a ligand or partner? Denatured during isolation?
Folding requires conditions found inside cells? Lack of folding encoded by amino acid
sequence?
Solution
IDPs (Intrinsically disordered protein) and IDRs (Intrinsically disordered regions) lack structure
due to lack of folding encoded by amino acid seuence. In general, IDPs are characterized by a
low content of bulky hydrophobic amino acids and a high proportion of polar and charged amino
acids, usually referred to as low hydrophobicity. This property leads to good interactions with
water. Furthermore, high net charges promote disorder because of electrostatic repulsion
resulting from equally charged residues. Thus disordered sequences cannot sufficiently bury a
hydrophobic core to fold into stable globular proteins. Some proteins are fully disordered while
some are partial. Partial disordered proteins have some disordered regions (IDRs). Hence, IDPs
and IDRs have no fix structure and cover a spectrum of states from fully unstructured to partially
structured and include random coils, (pre-)molten globules, and large multi-domain proteins
connected by flexible linkers.