Conditionally and Transiently Disordered Proteins: Awakening Cryptic Disorder To Regulate Protein Function

Jakob, Ursula; Kriwacki, Richard W.; Uversky, Vladimir N.

doi:10.1021/cr400459c

Cited by 175 publications

(181 citation statements)

References 377 publications

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“…HdeA and HdeB are typical members of a growing group of so-called "conditionally disordered chaperones" that use stress-induced unfolding to trigger chaperone-client interactions and chaperoning activation. The disorder-based interactions enable them to protect a broad array of client proteins with the same interacting interface (30,31); however, these disordered interfaces should be under tight control to avoid toxic nonspecific interactions, including self-aggregation (32).…”

Section: Discussionmentioning

confidence: 99%

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Comparative proteomics reveal distinct chaperone–client interactions in supporting bacterial acid resistance

Zhang

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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HdeA and HdeB constitute the essential chaperone system that functions in the unique periplasmic space of Gram-negative enteric bacteria to confer acid resistance. How this two-chaperone machinery cooperates to protect a broad range of client proteins from acid denaturation while avoiding nonspecific binding during bacterial passage through the highly acidic human stomach remains unclear. We have developed a comparative proteomic strategy that combines the genetically encoded releasable protein photocross-linker with 2D difference gel electrophoresis, which allows an unbiased side-by-side comparison of the entire client pools from these two acid-activated chaperones in Escherichia coli. Our results reveal distinct client specificities between HdeA and HdeB in vivo that are determined mainly by their different responses to pH stimulus. The intracellular acidity serves as an environmental cue to determine the folding status of both chaperones and their clients, enabling specific chaperone-client binding and release under defined pH conditions. This cooperative and synergistic mode of action provides an efficient, economical, flexible, and finely tuned protein quality control strategy for coping with acid stress.comparative proteomics | conditionally disordered chaperones | bacteria acid resistance | 2D-DIGE | photocross-linking

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Section: Discussionmentioning

confidence: 99%

“…A number of stress-specific chaperones that specifically activate their chaperone functions through stress-induced conformational rearrangements, unfolding or changes in oligomerization states have been identified (30,31). The stress conditions also may contribute to the tight control of their client profiles, thereby avoiding nonspecific binding.…”

mentioning

confidence: 99%

Comparative proteomics reveal distinct chaperone–client interactions in supporting bacterial acid resistance

Zhang

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been recently emphasized that functions of some ordered proteins rely on the decrease in the amount of their ordered structure [97]. In other words, these ordered proteins require local or even global functional unfolding, which has induced nature and transient character [97].…”

Section: Protein Complexes and Dormant Disordermentioning

confidence: 99%

The multifaceted roles of intrinsic disorder in protein complexes

2015

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Edited by Wilhelm Just Keywords:Intrinsically disordered protein Intrinsically disordered protein region Protein-protein interaction Protein complex Scaffold Regulation Polyvalent interaction a b s t r a c t Intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs) are important constituents of many protein complexes, playing various structural, functional, and regulatory roles. In such disorder-based protein complexes, functional disorder is used both internally (for assembly, movement, and functional regulation of the different parts of a given complex) and externally (for interactions of a complex with its external regulators). In complex assembly, IDPs/IDPRs serve as the molecular glue that cements complexes or as highly flexible scaffolds. Disorder defines the order of complex assembly and the ability of a protein to be involved in polyvalent interactions. It is at the heart of various binding mechanisms and interaction modes ascribed to IDPs. Disorder in protein complexes is related to multifarious applications of induced folding and induced functional unfolding, or defines the entropic chain activities, such as stochastic machines and binding rheostats. This review opens a FEBS Letters Special Issue on Dynamics, Flexibility, and Intrinsic Disorder in protein assemblies and represents a brief overview of intricate roles played by IDPs and IDPRs in various aspects of protein complexes.

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“…[1][2][3][4][5][6][7] Because of their lack of stable structures, exceptional spatiotemporal heterogeneity, outstanding conformational plasticity, ability to be precisely controlled and regulated, and capability to conduct and juggle multiple jobs, intrinsically disordered proteins (IDPs) and hybrid proteins possessing ordered domains and intrinsically disordered protein regions (IDPRs) 8 are specialized in unique biologic functions, [1][2][3][4][5][6][7] which are extending far beyond mostly catalytic activities traditionally assigned to the proteins within the "one gene -one structure -one function" paradigm. 1,3,[10][11][12]18,[39][40][41] In fact, among intrinsic disorder-based biologic functions are regulation of various cellular pathways, binding promiscuity, involvement in diverse signaling processes, and participation in cell protection, protein protection, controlled cell death, and cellular homeostasis. [1][2][3][4][5][6][7] Several recent studies (mostly of computational nature) revealed that IDPs are very common in various proteomes, with the proteome content of IDPs being typically an indicator of both evolution and adaptation to the environment.…”

Section: Introductionmentioning

confidence: 99%

Paradoxes and wonders of intrinsic disorder: Stability of instability

Uversky

2017

Intrinsically Disordered Proteins

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This article continues a series of short comments on the paradoxes and wonders of the protein intrinsic disorder phenomenon by introducing the "stability of instability" paradox. Intrinsically disordered proteins (IDPs) are characterized by the lack of stable 3D-structure, and, as a result, have an exceptional ability to sustain exposure to extremely harsh environmental conditions (an illustration of the "you cannot break what is already broken" principle). Extended IDPs are known to possess extreme thermal and acid stability and are able either to keep their functionality under these extreme conditions or to rapidly regain their functionality after returning to the normal conditions. Furthermore, sturdiness of intrinsic disorder and its capability to "ignore" harsh conditions provides some interesting and important advantages to its carriers, at the molecular (e.g., the cell wall-anchored accumulation-associated protein playing a crucial role in intercellular adhesion within the biofilm of Staphylococcus epidermidis), supramolecular (e.g., protein complexes, biologic liquid-liquid phase transitions, and proteinaceous membrane-less organelles), and organismal levels (e.g., the recently popularized case of the microscopic animals, tardigrades, or water bears, that use intrinsically disordered proteins to survive desiccation).

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Conditionally and Transiently Disordered Proteins: Awakening Cryptic Disorder To Regulate Protein Function

Cited by 175 publications

References 377 publications

Comparative proteomics reveal distinct chaperone–client interactions in supporting bacterial acid resistance

Comparative proteomics reveal distinct chaperone–client interactions in supporting bacterial acid resistance

The multifaceted roles of intrinsic disorder in protein complexes

Paradoxes and wonders of intrinsic disorder: Stability of instability

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