The functional importance of structure in unstructured protein regions

Davey, Norman E.

doi:10.1016/j.sbi.2019.03.009

Cited by 83 publications

(78 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, some RBPs recognize RNA secondary structure, sequence elements present within structural elements, or a combination of the two. Many RBPs also contain intrinsically disordered regions (IDRs) that could regulate the assembly and dynamics of RNP complexes 108 . Most of the RBPs involved in localization have been identified through genetic screens and/or affinity purification of proteins that bind the localized transcript.…”

Section: Role Of Cis and Trans Factors In Rna Localizationmentioning

confidence: 99%

Mechanisms and consequences of subcellularRNAlocalization across diverse cell types

Engel

Arora

Goering

et al. 2020

Traffic

View full text Add to dashboard Cite

Essentially all cells contain a variety of spatially restricted regions that are important for carrying out specialized functions. Often, these regions contain specialized transcriptomes that facilitate these functions by providing transcripts for localized translation. These transcripts play a functional role in maintaining cell physiology by enabling a quick response to changes in the cellular environment. Here, we review how RNA molecules are trafficked within cells, with a focus on the subcellular locations to which they are trafficked, mechanisms that regulate their transport and clinical disorders associated with misregulation of the process. K E Y W O R D SRNA binding protein, RNA cis-element, RNA localization, RNA transport, zipcode

show abstract

Section: Role Of Cis and Trans Factors In Rna Localizationmentioning

confidence: 99%

Mechanisms and consequences of subcellularRNAlocalization across diverse cell types

Engel

Arora

Goering

et al. 2020

Traffic

View full text Add to dashboard Cite

show abstract

“…IDP research spans several experimental fields studying protein structure and function including structural biology, biophysics, biochemistry, cell biology, proteomics, comparative genomics, systems biology, synthetic biology and pharmacology ( Figure 1A) ( Blikstad & Ivarsson, 2015; Corbi-Verge & Kim, 2016; Felli & Pierattelli, 2015; Forman-Kay & Mittag, 2013; Plitzko et al , 2017). On a structural level, IDRs do not adopt a single stable highly populated structure, instead, they are structurally heterogeneous, continuously sample a wide ensemble of conformations, with preferentially sampled intramolecular contacts driving local transient secondary structure and compaction of conformations ( Davey, 2019; Dyson & Wright, 2005; Forman-Kay & Mittag, 2013; Holehouse & Pappu, 2018). Therefore, IDRs are more easily described by probabilistic models than the intuitive visual representations of structures of folded protein regions.…”

Section: Introductionmentioning

confidence: 99%

An intrinsically disordered proteins community for ELIXIR

et al. 2019

View full text Add to dashboard Cite

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) are now recognised as major determinants in cellular regulation. This white paper presents a roadmap for future e-infrastructure developments in the field of IDP research within the ELIXIR framework. The goal of these developments is to drive the creation of high-quality tools and resources to support the identification, analysis and functional characterisation of IDPs. The roadmap is the result of a workshop titled “An intrinsically disordered protein user community proposal for ELIXIR” held at the University of Padua. The workshop, and further consultation with the members of the wider IDP community, identified the key priority areas for the roadmap including the development of standards for data annotation, storage and dissemination; integration of IDP data into the ELIXIR Core Data Resources; and the creation of benchmarking criteria for IDP-related software. Here, we discuss these areas of priority, how they can be implemented in cooperation with the ELIXIR platforms, and their connections to existing ELIXIR Communities and international consortia. The article provides a preliminary blueprint for an IDP Community in ELIXIR and is an appeal to identify and involve new stakeholders.

show abstract

“…Largely ignored in evolutionary studies, except for a few exceptions (for example see [36][37][38] ), contact variations due to conformational changes are revealed as impossible to neglect in IDP ensembles. These variations impose cumulative constraints on evolutionary rates 39 that may reflect the importance of transitory or preferred conformations in the ensemble 13 .…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, the induced-fit model proposes that the adoption of the preferred conformation occurs after binding, in a process that may involve conformational changes and disorder-order transitions. Whatever the relative importance of these models to explain protein biology 12 , pre-existence of low-represented competent conformations or conformational 3 rearrangements after ligand binding, raise the notion that IDPs ensembles are not fully disordered and that conformations with residual structure content play key biological roles 5,[13][14][15][16] .…”

Section: Introductionmentioning

confidence: 99%

Intrinsically disordered protein ensembles shape evolutionary rates revealing conformational patterns

Palopoli

Marchetti

Monzón

et al. 2020

Preprint

View full text Add to dashboard Cite

Intrinsically disordered proteins (IDPs) lack stable tertiary structure under physiological conditions. The unique composition and complex dynamical behaviour of IDPs make them a challenge for structural biology and molecular evolution studies. Using NMR ensembles, we found that IDPs evolve under a strong site-specific evolutionary rate heterogeneity, mainly originated by different constraints derived from their inter-residue contacts. Evolutionary rate profiles correlate with the experimentally observed conformational diversity of the protein, allowing the description of different conformational patterns possibly related to their structure-function relationships. The correlation between evolutionary rates and contact information improves when structural information is taken not from any individual conformer or the whole ensemble, but from combining a limited number of conformers. Our results suggest that residue contacts in disordered regions constrain evolutionary rates to conserve the dynamic behaviour of the ensemble and that evolutionary rates can be used as a proxy for the conformational diversity of IDPs.

show abstract

The functional importance of structure in unstructured protein regions

Cited by 83 publications

References 82 publications

Mechanisms and consequences of subcellularRNAlocalization across diverse cell types

Mechanisms and consequences of subcellularRNAlocalization across diverse cell types

An intrinsically disordered proteins community for ELIXIR

Intrinsically disordered protein ensembles shape evolutionary rates revealing conformational patterns

Contact Info

Product

Resources

About