Proteome-wide signatures of function in highly diverged intrinsically disordered regions

Zarin, Taraneh; Strome, Bob; Ba, Alex N Nguyen; Alberti, Simon; Forman‐Kay, Julie D.; Moses, Alan M.

doi:10.7554/elife.46883

Cited by 161 publications

(175 citation statements)

References 124 publications

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“…The significance of this SLiM is indicated by its evolutionary conservation ( Fig. 1), despite its occurrence in an IDR where frequently positional conservation is not observed (67,68). We used CPMG RD (Fig.…”

Section: Discussionmentioning

confidence: 99%

Dysregulated interactions triggered by a neuropathy-causing mutation in the IPV motif of HSP27

Alderson

Adriaenssens

Asselbergh

et al. 2019

Preprint

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Molecular chaperone | small heat-shock protein | Charcot-Marie-Tooth disease | short linear motif | nuclear magnetic resonance | protein aggregation | neurological diseaseCorrespondence: vincent.timmerman@uantwerpen.be, andrew.baldwin@chem.ox.ac.uk, justin.benesch@chem.ox.ac.uk the backbone atoms of V111, T113, and L157 (Fig. 1E). In HSP27, the IxI/V motif corresponds to I181-P182-V183; the Ile and Val residues penetrate the β4/β8 groove while P182 does not make any direct contacts with the ACD (Fig. 1E).The P182L variant has impaired chaperone activity in vitro. We purified recombinant human HSP27 and the CMTimplicated P182L variant from E. coli, and compared their chaperone activities in vitro using a substrate aggregation assay. We tested their ability to prevent the aggregation of two model substrate proteins, malate dehydrogenase (MDH) and

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Section: Discussionmentioning

confidence: 99%

Dysregulated interactions triggered by a neuropathy-causing mutation in the IPV motif of HSP27

Alderson

Adriaenssens

Asselbergh

et al. 2019

Preprint

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“…IDRs are enriched in sites of posttranslational modifications and are often alternatively spliced [13], and may have conserved molecular features, such as subcellular localization, membrane transport, motor activity, ribosomal function, etc. [19]. Thus, IDPs/IDRs are good candidates for the conformational memory providing fast cellular learning ( Figure 1).…”

Section: Conformational Memorymentioning

confidence: 99%

Learning of Signaling Networks: Molecular Mechanisms

Csermely

Kunsic

Mendik

et al. 2020

Trends in Biochemical Sciences

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Molecular processes of neuronal learning have been well-described. However, learning mechanisms of non-neuronal cells have not been fully understood at the molecular level. Here, we discuss molecular mechanisms of cellular learning, including conformational memory of intrinsically disordered proteins and prions, signaling cascades, protein translocation, RNAs (microRNA and lncRNA), and chromatin memory. We hypothesize that these processes constitute the learning of signaling networks and correspond to a generalized Hebbian learning process of single, non-neuronal cells, and discuss how cellular learning may open novel directions in drug design and inspire new artificial intelligence methods. Highlights--Besides the well-known learning processes of neurons, non-neuronal single cells are able to learn and show a more robust (and often faster) adaptive response when the same stimulus is repeated.--Known examples of cellular learning are sensitization-or habituation-type responses.--Several molecular mechanisms of neuronal learning, such as conformational memory, protein translocation, signaling cascades, microRNAs, lncRNAs and chromatin memory, also participate in learning of non-neuronal, single cells.--We propose that these molecular mechanisms form the integrative memory of signaling networks and display a generalized Hebbian learning process by increasing those edge weights through which the signal has been propagated. Learning of non-neural cells: Adaptive Molecular Responses Observed when the same Stimulus is RepeatedMolecular mechanisms of neuronal learning have been well-established in the past decades [1]. However, we know relatively little about the molecular details of learning mechanisms of non-neuronal cells. We define cellular learning as an adaptive response to a simple stimulus observed when the same stimulus is repeated in a short time -as compared to the duration of the cell cycle of the given cell. We note that it is crucial to discriminate between molecular changes which are indeed adaptive, and those which are fortuitous by-products of other, co-* Correspondence: csermely.peter@med.semmelweis-univ.hu (P. Csermely)

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“…S5A). In a 5 recent analysis of yeast disordered segments (23), several of the endocytosis/actin proteins had multiple properties (16) within disordered regions that were similar to Sec31 (Fig. S5B).…”

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confidence: 93%

A multivalent fuzzy interface drives reversible COPII coat assembly

Miller

Stancheva

Hutchings

et al. 2020

Preprint

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Protein secretion is initiated at the endoplasmic reticulum by the COPII coat, which selfassembles to form vesicles. Here, we examine the mechanisms by which the outer scaffolding layer of the coat drives local assembly of a structure rigid enough to enforce membrane curvature, yet able to readily disassemble at the Golgi. An intrinsically 15 disordered region in the outer coat protein, Sec31, drives binding with an inner coat layer via multiple distinct interfaces. Interactions are individually dispensable but combinatorially reinforce each other, suggesting coat oligomerization is driven by the cumulative effects of multivalent interactions. Such a multimodal assembly platform could be readily reversed at the Golgi via perturbation of each individual interface. These design principles provide an 20 explanation for how cells build a powerful yet transient scaffold to direct vesicle traffic.

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Proteome-wide signatures of function in highly diverged intrinsically disordered regions

Cited by 161 publications

References 124 publications

Dysregulated interactions triggered by a neuropathy-causing mutation in the IPV motif of HSP27

Dysregulated interactions triggered by a neuropathy-causing mutation in the IPV motif of HSP27

Learning of Signaling Networks: Molecular Mechanisms

A multivalent fuzzy interface drives reversible COPII coat assembly

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