Large-scale analysis of redox-sensitive conditionally disordered protein regions reveal their widespread nature and key roles in high-level eukaryotic processes

Gábor Erdos; Bálint Mészáros; Dana Reichmann; Zsuzsanna Dosztányi

Several members of the ribosome were also shown to be redox-sensitive, further containing predicted conditionally disordered regions. This group includes the mitochondrial Mrpl32, which was shown to undergo redox-dependent regulation [43] . Members of the cytosolic ribonucleoprotein complex were also included in this group (RPL37A, RPL37B, RPS29A, RPS29B, RPL40A, RPL40B). In addition, MAK16 is involved in the biogenesis of the ribosomal large subunit in the nucleolus. The common structural theme among these proteins is Zn 2+ binding, typically involving a specific zinc finger class, called treble clefs. Additional members of the translation machinery are also candidates for redox-regulated conditional disorder mediated by their Zn 2+ binding domains, such as Taf1 and Elf1. Taf1 is a zinc knuckle that plays a central role in TFIID promoter binding and regulation of transcription initiation [44] . Elf1 is a conserved transcription elongation factor that contains a putative zinc binding domain with four conserved cysteines [45] . Another Zn 2+ binding protein, Gis2 interacts with the mRNA translation machinery and is a component of the stress induced RNP granules [46] . NRP1 also belongs to the group of Zn 2+ finger proteins, with a currently uncharacterized RNA binding function, also localizing to stress granules. From a functional point of view, the redox-sensitivity of these proteins can play a critical role in the global attenuation of translation in response to oxidative stress [40] . Further candidates for redox-regulated conditional disorder include other Zn 2+ binding proteins, such as the DNA damage-responsive transcriptional repressor RPH1, Pre-mRNA-splicing factor RDS3 and DNA-directed RNA polymerases I, II, and III subunit RPABC4 (Table 1) .