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

Gao, Chao; Ma, Chengbin; Wang, Huqiang; Zhong, Haolin; Zang, Jiayin; Zhong, Rugang; He, Fuchu; Yang, Dong

doi:10.1038/s41598-021-82656-9

Cited by 25 publications

(29 citation statements)

References 73 publications

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“…Why are bacterial condensates soluble within a much lower ATP range (0.5-1 mM) compared to eukaryotic condensates? It has been observed that the intrinsic disorder content of a proteome is correlated with cellular complexity (31). Thus, we posit that the emergent ATP-dependent multivalency in disordered proteins has been preserved through evolution due to a concomitant increase in cellular complexity and energy consumption.…”

Section: Discussionmentioning

confidence: 85%

ATP-responsive biomolecular condensates tune bacterial kinase signaling

Saurabh

Chong

Bayas

et al. 2020

Preprint

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Maintenance of robust biochemical signaling is essential for oligotrophic bacteria that survive under fluctuating environmental challenges. We report that a polar microdomain in Caulobacter crescentus tunes a critical signaling pathway to nutrient availability using the hydrotrope effect of ATP on an intracellular biomolecular condensate. Sequestration of this signaling pathway within a specialized polar microdomain formed by two interacting membraneless organelles, stimulates the activity of a localized kinase, which is dependent on the phase transition parameters of a disordered protein component of the microdomain. Under low ATP concentrations, phase separation in the microdomain is reinforced, enhancing kinase activity, and thereby conferring control of a critical cell cycle signaling pathway to the physical properties of a unique system of membraneless organelles.

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Section: Discussionmentioning

confidence: 85%

ATP-responsive biomolecular condensates tune bacterial kinase signaling

Saurabh

Chong

Bayas

et al. 2020

Preprint

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“…Among them, more than two-thirds are NonDomCDRPs, while only a small fraction (less than10%) are DomCDRPs. Protein domains containing CDRs may play an important role in increasing organism complexity [ 5 ], indicating that DomCDRs and DomCDRPs may have special functions. Thus, the property differences among these two types of CDRs and four types of proteins were investigated in this study.…”

Section: Resultsmentioning

confidence: 99%

“…The CDRs in IDPs play an important role in the transition of structure and function, contributing to the formation of functional diversity and system complexity [ 4 ]. Previous studies have found that CDRs may be located inside or outside the protein domains (referring to all Pfam-A domains in this study) [ 1 , 5 , 6 , 7 ]. According to the relative location, CDRs are divided into two types: CDRs inside protein domains (DomCDRs) and CDRs outside protein domains (NonDomCDRs) ( Figure 1 A).…”

Section: Introductionmentioning

confidence: 91%

“…CDR-containing protein domains are an important contributor to the formation of organism complexity, since there is a significant positive correlation between the proportion of CDR-containing domain families and the organism complexity as measured by cell-type number [ 5 ]. Thus, which CDR-containing protein domains are related to the formation of biological complexity?…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Zhong

Gao

et al. 2021

IJMS

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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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“…The key domains of P that mediate Negri body appearance in complex with N were narrowed down by mutational approaches to the dimerization domain, the amino-terminal part of its second intrinsically disordered domain (IDD2) as well as the C-terminus. IDDs in general have no stable three-dimensional structure, but instead show a high degree in flexibility that can result in binding to other proteins or RNA, as well as in post-translational modifications like phosphorylation [120]. In this regard, IDD1 and IDD2 of P are flanking a dimerization domain (DD) and, like the C-terminus, are phosphorylated.…”

Section: Rhabdoviridae: Ibs Of Rabv and Vsvmentioning

confidence: 99%

New Perspectives on the Biogenesis of Viral Inclusion Bodies in Negative-Sense RNA Virus Infections

Dolnik

Gerresheim

Biedenkopf

2021

Cells

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Infections by negative strand RNA viruses (NSVs) induce the formation of viral inclusion bodies (IBs) in the host cell that segregate viral as well as cellular proteins to enable efficient viral replication. The induction of those membrane-less viral compartments leads inevitably to structural remodeling of the cellular architecture. Recent studies suggested that viral IBs have properties of biomolecular condensates (or liquid organelles), as have previously been shown for other membrane-less cellular compartments like stress granules or P-bodies. Biomolecular condensates are highly dynamic structures formed by liquid-liquid phase separation (LLPS). Key drivers for LLPS in cells are multivalent protein:protein and protein:RNA interactions leading to specialized areas in the cell that recruit molecules with similar properties, while other non-similar molecules are excluded. These typical features of cellular biomolecular condensates are also a common characteristic in the biogenesis of viral inclusion bodies. Viral IBs are predominantly induced by the expression of the viral nucleoprotein (N, NP) and phosphoprotein (P); both are characterized by a special protein architecture containing multiple disordered regions and RNA-binding domains that contribute to different protein functions. P keeps N soluble after expression to allow a concerted binding of N to the viral RNA. This results in the encapsidation of the viral genome by N, while P acts additionally as a cofactor for the viral polymerase, enabling viral transcription and replication. Here, we will review the formation and function of those viral inclusion bodies upon infection with NSVs with respect to their nature as biomolecular condensates.

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

Cited by 25 publications

References 73 publications

ATP-responsive biomolecular condensates tune bacterial kinase signaling

ATP-responsive biomolecular condensates tune bacterial kinase signaling

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

New Perspectives on the Biogenesis of Viral Inclusion Bodies in Negative-Sense RNA Virus Infections

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