Faculty Opinions recommendation of Fairy "tails": flexibility and function of intrinsically disordered extensions in the photosynthetic world.

Abstract Understanding the interplay between sequence, structure and function of proteins has been complicated in recent years by the discovery of intrinsically disordered proteins (IDPs), which perform biological functions in the absence of a well-defined three-dimensional fold. Disordered protein sequences account for roughly 30% of the human proteome and in many proteins, disordered and ordered domains coexist. However, few studies have assessed how either feature affects the properties of the other. In this study, we examine the role of a disordered tail in the overall properties of the two-domain, calcium-sensing protein neuronal calcium sensor 1 (NCS-1). We show that loss of just six of the 190 residues at the flexible C-terminus is sufficient to severely affect stability, dynamics, and folding behavior of both ordered domains. We identify specific hydrophobic contacts mediated by the disordered tail that may be responsible for stabilizing the distal N-terminal domain. Moreover, sequence analyses indicate the presence of an LSL-motif in the tail that acts as a mimic of native ligands critical to the observed order–disorder communication. Removing the disordered tail leads to a shorter life-time of the ligand-bound complex likely originating from the observed destabilization. This close relationship between order and disorder may have important implications for how investigations into mixed systems are designed and opens up a novel avenue of drug targeting exploiting this type of behavior.

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Intrinsic disorder in protein domains contributes to both organism complexity and clade-specific functions

Scientific Reports ◽

10.1038/s41598-021-82656-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Chao Gao ◽

Chong Ma ◽

Huqiang Wang ◽

Haolin Zhong ◽

Jiayin Zang ◽

...

Keyword(s):

Biological Significance ◽

Protein Domains ◽

Functional Requirements ◽

Post Translational Modification ◽

Intrinsically Disordered ◽

Genome Wide ◽

Complex Functions ◽

Disorder Degree ◽

Functional Features ◽

And Function

AbstractInterestingly, some protein domains are intrinsically disordered (abbreviated as IDD), and the disorder degree of same domains may differ in different contexts. However, the evolutionary causes and biological significance of these phenomena are unclear. Here, we address these issues by genome-wide analyses of the evolutionary and functional features of IDDs in 1,870 species across the three superkingdoms. As the result, there is a significant positive correlation between the proportion of IDDs and organism complexity with some interesting exceptions. These phenomena may be due to the high disorder of clade-specific domains and the different disorder degrees of the domains shared in different clades. The functions of IDDs are clade-specific and the higher proportion of post-translational modification sites may contribute to their complex functions. Compared with metazoans, fungi have more IDDs with a consecutive disorder region but a low disorder ratio, which reflects their different functional requirements. As for disorder variation, it’s greater for domains among different proteins than those within the same proteins. Some clade-specific ‘no-variation’ or ‘high-variation’ domains are involved in clade-specific functions. In sum, intrinsic domain disorder is related to both the organism complexity and clade-specific functions. These results deepen the understanding of the evolution and function of IDDs.

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Bioinformatics Approaches to the Structure and Function of Intrinsically Disordered Proteins

From Protein Structure to Function with Bioinformatics ◽

10.1007/978-1-4020-9058-5_5 ◽

2008 ◽

pp. 113-140 ◽

Cited By ~ 1

Author(s):

Peter Tompa

Keyword(s):

Intrinsically Disordered Proteins ◽

Structure And Function ◽

Disordered Proteins ◽

Intrinsically Disordered ◽

And Function

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Expanding the Disorder-Function Paradigm in the C-Terminal Tails of Erbbs

Biomolecules ◽

10.3390/biom11111690 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1690

Author(s):

Louise Pinet ◽

Nadine Assrir ◽

Carine van Heijenoort

Keyword(s):

Tyrosine Kinases ◽

Kinase Domain ◽

Cellular Motility ◽

Dynamic Features ◽

Sh2 Domains ◽

Intrinsically Disordered ◽

Src Homology ◽

Regulation Functions ◽

And Function

ErbBs are receptor tyrosine kinases involved not only in development, but also in a wide variety of diseases, particularly cancer. Their extracellular, transmembrane, juxtamembrane, and kinase folded domains were described extensively over the past 20 years, structurally and functionally. However, their whole C-terminal tails (CTs) following the kinase domain were only described at atomic resolution in the last 4 years. They were shown to be intrinsically disordered. The CTs are known to be tyrosine-phosphorylated when the activated homo- or hetero-dimers of ErbBs are formed. Their phosphorylation triggers interaction with phosphotyrosine binding (PTB) or Src Homology 2 (SH2) domains and activates several signaling pathways controling cellular motility, proliferation, adhesion, and apoptosis. Beyond this passive role of phosphorylated domain and site display for partners, recent structural and function studies unveiled active roles in regulation of phosphorylation and interaction: the CT regulates activity of the kinase domain; different phosphorylation states have different compaction levels, potentially modulating the succession of phosphorylation events; and prolines have an important role in structure, dynamics, and possibly regulatory interactions. Here, we review both the canonical role of the disordered CT domains of ErbBs as phosphotyrosine display domains and the recent findings that expand the known range of their regulation functions linked to specific structural and dynamic features.

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Intrinsically disordered proteins identified in the aggregate proteome serve as biomarkers of neurodegeneration

Metabolic Brain Disease ◽

10.1007/s11011-021-00791-8 ◽

2021 ◽

Author(s):

Srinivas Ayyadevara ◽

Akshatha Ganne ◽

Meenakshisundaram Balasubramaniam ◽

Robert J. Shmookler Reis

Keyword(s):

Intrinsically Disordered Proteins ◽

Protein Complexes ◽

Disordered Proteins ◽

Intrinsically Disordered ◽

Intrinsically Disordered Regions ◽

Physiological Processes ◽

Protein Partners ◽

And Function ◽

Computational Analyses ◽

Disordered Regions

AbstractA protein’s structure is determined by its amino acid sequence and post-translational modifications, and provides the basis for its physiological functions. Across all organisms, roughly a third of the proteome comprises proteins that contain highly unstructured or intrinsically disordered regions. Proteins comprising or containing extensive unstructured regions are referred to as intrinsically disordered proteins (IDPs). IDPs are believed to participate in complex physiological processes through refolding of IDP regions, dependent on their binding to a diverse array of potential protein partners. They thus play critical roles in the assembly and function of protein complexes. Recent advances in experimental and computational analyses predicted multiple interacting partners for the disordered regions of proteins, implying critical roles in signal transduction and regulation of biological processes. Numerous disordered proteins are sequestered into aggregates in neurodegenerative diseases such as Alzheimer’s disease (AD) where they are enriched even in serum, making them good candidates for serum biomarkers to enable early detection of AD.

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The Distinct Properties of the Consecutive Disordered Regions Inside or Outside Protein Domains and Their Functional Significance

International Journal of Molecular Sciences ◽

10.3390/ijms221910677 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10677

Author(s):

Huqiang Wang ◽

Haolin Zhong ◽

Chao Gao ◽

Jiayin Zang ◽

Dong Yang

Keyword(s):

Intrinsically Disordered Proteins ◽

Protein Domains ◽

Comprehensive Analysis ◽

Disordered Proteins ◽

Functional Constraints ◽

Biological Functions ◽

Post Translational Modification ◽

Intrinsically Disordered ◽

And Function ◽

Disordered Regions

The consecutive disordered regions (CDRs) are the basis for the formation of intrinsically disordered proteins, which contribute to various biological functions and increasing organism complexity. Previous studies have revealed that CDRs may be present inside or outside protein domains, but a comprehensive analysis of the property differences between these two types of CDRs and the proteins containing them is lacking. In this study, we investigated this issue from three viewpoints. Firstly, we found that in-domain CDRs are more hydrophilic and stable but have less stickiness and fewer post-translational modification sites compared with out-domain CDRs. Secondly, at the protein level, we found that proteins with only in-domain CDRs originated late, evolved rapidly, and had weak functional constraints, compared with the other two types of CDR-containing proteins. Proteins with only in-domain CDRs tend to be expressed spatiotemporal specifically, but they tend to have higher abundance and are more stable. Thirdly, we screened the CDR-containing protein domains that have a strong correlation with organism complexity. The CDR-containing domains tend to be evolutionarily young, or they changed from a domain without CDR to a CDR-containing domain during evolution. These results provide valuable new insights about the evolution and function of CDRs and protein domains.

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