Abstract:

Intrinsically disordered regions (IDRs) in proteins are highly abundant, but they are still commonly viewed as long stretches of polar, solvent accessible residues. Here we show that the disordered C-terminal domain of HIV-1 Rev has two sub-regions that carry out two distinct complementary roles of regulating oligomerization and contributing to stability. We propose this is carried out by a delicate balance between charged and hydrophobic residues within the IDR. We suggest that intrinsically disordered regions in proteins should be divided to sub domains similarly to structured regions, rather than being viewed as a long flexible stretches. This implicates that mutations in IDRs can affect protein function in disease just like known mutations in structured regions.