Disordered Proteinaceous Machines

Fuxreiter, Mónika; Tóth-Petróczy, Ágnes; Kraut, Daniel A.; Matouschek, Andreas T; Lim, Roderick Y. H.; Xue, Bin; Kurgan, Lukasz; Uversky, Vladimir N.

doi:10.1021/cr4007329

Cited by 122 publications

(94 citation statements)

References 507 publications

(1,098 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…131 In fact, mutual folding of intrinsically disordered protomers is crucial for the formation of so-called 2-state protein complexes, where the protomers are intrinsically disordered in their unbound forms and undergo the binding-induced folding at the complex formation. [132][133][134][135] Structurally, the protomers of protein complexes formed via the 2-state mechanism, where binding and folding occur concomitantly, are characterized by very large per-residue interface and surface areas. 134 As a result, protomers in such complexes do not have a simple globular structure (i.e., structure that defines the smallest accessible area), but possess very unusual, mostly non-globular shapes.…”

Section: Making Sturdy Complexesmentioning

confidence: 99%

Paradoxes and wonders of intrinsic disorder: Stability of instability

Uversky

2017

Intrinsically Disordered Proteins

Self Cite

View full text Add to dashboard Cite

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).

show abstract

Section: Making Sturdy Complexesmentioning

confidence: 99%

Paradoxes and wonders of intrinsic disorder: Stability of instability

Uversky

2017

Intrinsically Disordered Proteins

Self Cite

View full text Add to dashboard Cite

show abstract

“…IDP-based complex formation frequently involves at least partial folding of IDPR(s) into specific structures [16,17,[29][30][31]37,[40][41][42][43][44][45], and the disorder-based interactions are characterized by adaptability, promiscuity, and ability of a given IDPR to fold differently upon binding to different targets [12,32]. Also, the ability of an IDP to partially fold at interaction with its binding partner(s) opens a possibility of the ''binding chain reaction'' mechanism based on the sequential generation of novel binding sites by partial folding of new disordered partners engaged in the consecutive interaction with the existing complex [37].…”

Section: Disorder and Binding Chain Reactionsmentioning

confidence: 99%

“…Also, the ability of an IDP to partially fold at interaction with its binding partner(s) opens a possibility of the ''binding chain reaction'' mechanism based on the sequential generation of novel binding sites by partial folding of new disordered partners engaged in the consecutive interaction with the existing complex [37]. This model is illustrated by Fig.…”

Section: Disorder and Binding Chain Reactionsmentioning

confidence: 99%

“…In fact, IDPRs are needed for the multiform binding mechanism, where the complex formation between an IDP and its ordered target leads to conformational changes in a target and to the opening of a hidden binding site [37,45]. Here, a protein complex is formed sequentially, in a stepwise manner, via the emergence of binding intermediates which leads to the structural rearrangements in a partner molecule accompanied by the exposure of ''hidden'' binding site, which are accessible to an IDP due to its structural flexibility [45].…”

Section: Role Of Intrinsic Disorder In the Multiform Binding Mechanismmentioning

confidence: 99%

See 1 more Smart Citation

The multifaceted roles of intrinsic disorder in protein complexes

2015

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Regardless, what is clear is that the FG Nups -being intrinsically disordered -are sensitive to experimental design in vitro, and can adopt different morphologies at different length scales with diverse structures, characteristics and properties. 24 We refer the interested reader to ref. 24 for a recent review on the matter.…”

Section: Introductionmentioning

confidence: 99%