A creature with a hundred waggly tails: intrinsically disordered proteins in the ribosome

Abstract

Intrinsic disorder (i.e., lack of a unique 3-D structure) is a common phenomenon, and many biologically active proteins are disordered as a whole, or contain long disordered regions. These intrinsically disordered proteins/regions constitute a significant part of all proteomes, and their functional repertoire is complementary to functions of ordered proteins. In fact, intrinsic disorder represents an important driving force for many specific functions. An illustrative example of such disorder-centric functional class is RNA-binding proteins. In this study, we present the results of comprehensive bioinformatics analyses of the abundance and roles of intrinsic disorder in 3,411 ribosomal proteins from 32 species. We show that many ribosomal proteins are intrinsically disordered or hybrid proteins that contain ordered and disordered domains. Predicted globular domains of many ribosomal proteins contain noticeable regions of intrinsic disorder. We also show that disorder in ribosomal proteins has different characteristics compared to other proteins that interact with RNA and DNA including overall abundance, evolutionary conservation, and involvement in protein-protein interactions. Furthermore, intrinsic disorder is not only abundant in the ribosomal proteins, but we demonstrate that it is absolutely necessary for their various functions.

Deletion of L4 domains reveals insights into the importance of ribosomal protein extensions in eukaryotic ribosome assembly

“…In the process, the unstructured loop of L4 possibly transitions to a folded state similar to what is found in the structures of mature 60S subunits (Ben-Shem et al 2011). Our results support prevailing models that depict coupled binding and folding of r-protein extensions with rRNA during ribosome biogenesis (Klein et al 2004;Timsit et al 2009;Peng et al 2014). Moreover, consistent with the late pre-rRNA processing defect observed when the internal loop of L4 is removed, recent studies demonstrate that the functionally important centers of ribosomal subunits are assembled during later stages in assembly (Bussiere et al 2012;Strunk et al 2012;Karbstein 2013;Gamalinda et al 2014;Garcia-Gomez et al 2014).…”

“…Recent atomic structures of eukaryotic ribosomes showed that in contrast to the conserved internal r-protein extensions that penetrate the core, eukaryote-specific tails mainly thread across the surface of the ribosome (Ben-Shem et al 2011). These internal loops and external tails of r-proteins are intrinsically disordered; hence, the current model is that r-protein extensions chaperone co-folding of rRNA and/or stabilize tertiary interactions during assembly (Wilson and Nierhaus 2005;Timsit et al 2009;Peng et al 2014). However, the overarching function of r-protein extensions in the eukaryotic ribosome, especially regions not present in bacteria, remains to be established.…”

“…Similarly, only a handful of mutant alleles have been identified demonstrating that the conserved extended domains of eukaryotic r-proteins are important for ribosomal subunit formation (Jakovljevic et al 2004;Bussiere et al 2012;Garcia-Gomez et al 2014). Although flexible extensions are prevalent in r-proteins, there is a lack of information about their biological significance, which has largely been inferred computationally (Peng et al 2014). Here, we investigated two prominent extended domains of L4 in the yeast, Saccharomyces cerevisiae.…”

Exceptionally abundant exceptions: comprehensive characterization of intrinsic disorder in all domains of life

“…Consequently, we had to exclude viruses that were not considered in Ref. [47] and archaea that had small sample size.Similarly as in [48,49], we quantified the sequence conservation using relative entropy [50], which was computed from the Weighted Observed Percentages (WOP) profiles produced by PSI-BLAST [51]. PSI-BLAST was run with default parameters (−j 3, −h 0.001) against the nr database.…”

The N-terminal extension of yeast ribosomal protein L8 is involved in two major remodeling events during late nuclear stages of 60S ribosomal subunit assembly

“…Such extended domains are enriched in RNA interacting proteins, suggesting roles in the assembly, structure, and function of many different RNPs (Cumberworth et al 2013;Van Der Lee et al 2014). For example, 38 of the 78 r-proteins in yeast contain such extensions (Peng et al 2014). In the ribosome, disordered regions of r-proteins have been suggested to function as stabilizers of the tertiary structure of rRNA, as RNA chaperones to avoid kinetic traps, and as binding sites of dedicated assembly chaperones (Tompa 2003;Tompa and Csermely 2004;Van Der Lee et al 2014).…”