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{{afc comment|1=You need to write paragraphs of prose - not bulleted lists - that explain what this is all about. Lists of people without explanations what each of them have to do with the topic are meaningless. Write an '''article''' not a "powerpoint presentation". By the way - a "See also" list is only supposed to contain links to other relevant articles here on the English Wikipedia. I have requested [[WP:WikiProject Molecular and Cellular Biology]] members to take a look here and assist you with this article. [[User:Dodger67|Roger (Dodger67)]] ([[User talk:Dodger67|talk]]) 18:45, 10 March 2014 (UTC)}}
{{afc comment|1=You need to write paragraphs of prose - not bulleted lists - that explain what this is all about. Lists of people without explanations what each of them have to do with the topic are meaningless. Write an '''article''' not a "powerpoint presentation". By the way - a "See also" list is only supposed to contain links to other relevant articles here on the English Wikipedia. I have requested [[WP:WikiProject Molecular and Cellular Biology]] members to take a look here and assist you with this article. [[User:Dodger67|Roger (Dodger67)]] ([[User talk:Dodger67|talk]]) 18:45, 10 March 2014 (UTC)}}


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Protein function was originially thought to depend on a fixed threedimensional (3D) structure. This dogm has been challenged over the last decades by exponentially increasing evidence from various branches of structural biology as briefly outlined below. Next to ordered proteins, so-called Intrinsically Disordered Proteins (IDPs) are a very large and functionally important class of proteins.
Protein function was originially thought to depend on a fixed threedimensional (3D) structure. This dogm has been challenged over the last decades by exponentially increasing evidence from various branches of structural biology as briefly outlined below. Next to ordered proteins, so-called Intrinsically Disordered Proteins (IDPs) are a very large and functionally important class of proteins.

== History and background ==
== History and background ==


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>[[Anfinsen's Dogma]] (1973): (some) small proteins can fold spontaneously.<ref>{{cite pmid|4124164}}</ref>
>[[Anfinsen's Dogma]] (1973): (some) small proteins can fold spontaneously.<ref>{{cite pmid|4124164}}</ref>

>x-ray crystallographic evidence (1950s-now): large protein regions cannot be assigned in the electron density maps, which suggests that they are not fixed at unique positions relative to the crystal lattice or in other words that they are "disordered".
>x-ray crystallographic evidence (1950s-now): large protein regions cannot be assigned in the electron density maps, which suggests that they are not fixed at unique positions relative to the crystal lattice or in other words that they are "disordered".


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>bioinformatic predictions of intrinsic disorder in proteins (~2001): intrinsic disorder is more common in sequenced/predicted proteomes than in the latest PDB update.<ref>{{cite pmid|11381529}}</ref>
>bioinformatic predictions of intrinsic disorder in proteins (~2001): intrinsic disorder is more common in sequenced/predicted proteomes than in the latest PDB update.<ref>{{cite pmid|11381529}}</ref>
⚫
>IDPs are highly abundant among disease-related proteins: birth of the D2 concept (2008).<ref>{{cite pmid|18573080}}</ref>

⚫
>IDPs are highly abundant among disease-related proteins: birth of the D2 concept (2008) <ref>{{cite pmid|18573080}}</ref>.

== Definition ==
== Definition ==


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*bulk methods to study IDPs include: [[SAXS]] for ensemble shape information, [[NMR]] for atomistic ensemble refinement, [[Fluorescence]] for visualising molecular interactions and conformational transitions, x-ray crystallography to highlight more mobile regions in otherwise rigid protein crystals, cryo-EM to reveal less fixed parts of proteins, light scattering to monitor size distributions of IDPs or their aggregation kinetics, [[Circular Dichroism]] to monitor secondary structure of IDPs,..
*bulk methods to study IDPs include: [[SAXS]] for ensemble shape information, [[NMR]] for atomistic ensemble refinement, [[Fluorescence]] for visualising molecular interactions and conformational transitions, x-ray crystallography to highlight more mobile regions in otherwise rigid protein crystals, cryo-EM to reveal less fixed parts of proteins, light scattering to monitor size distributions of IDPs or their aggregation kinetics, [[Circular Dichroism]] to monitor secondary structure of IDPs,..
*single-molecule methods to study IDPs include: spFRET<ref>{{cite pmid|24432838}}</ref> to study conformational flexibilty of IDPs and the kinetics of structural transitions, [[optical tweezers]]<ref>{{cite pmid|24475132}}</ref> for high-resolution insights into the ensembles of IDPs and their oligomers or aggregates, nanopores<ref>{{cite pmid|23327569}}</ref> to unveal global shape distributions of IDPs, magnetic tweezers<ref>{{cite pmid|23591872}}</ref> to study structural transitions for long times at low forces, high-speed [[AFM]] <ref>{{cite pmid|18698566}}</ref> to visualise the spatiotemporal flexibility of IDPs directly.
*single-molecule methods to study IDPs include: spFRET<ref>{{cite pmid|24432838}}</ref> to study conformational flexibilty of IDPs and the kinetics of structural transitions, [[optical tweezers]]<ref>{{cite pmid|24475132}}</ref> for high-resolution insights into the ensembles of IDPs and their oligomers or aggregates, nanopores<ref>{{cite pmid|23327569}}</ref> to unveal global shape distributions of IDPs, magnetic tweezers<ref>{{cite pmid|23591872}}</ref> to study structural transitions for long times at low forces, high-speed [[AFM]] <ref>{{cite pmid|18698566}}</ref> to visualise the spatiotemporal flexibility of IDPs directly.

== Biological Functions Enriched in IDPs ==

IDPs are enriched in hubs and scaffolds and regulate many cell-regulatory networks. A possible explanation for this fact is that IDPs often have larger surfaces for forming protein interfaces and change specific partners.


== Pioneering IDP labs ==
== Pioneering IDP labs ==



* Experimental and computational labs focusing on IDPs:
* Experimental and computational labs focusing on IDPs:
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== See also ==
== See also ==

[https://en.wikipedia.org/wiki/Intrinsically_unstructured_proteins]
[[Intrinsically_unstructured_proteins]]
[http://proteopedia.org/wiki/index.php/Intrinsically_Disordered_Protein]
[http://proteopedia.org/wiki/index.php/Intrinsically_Disordered_Protein]
* IDP journal: www.landes.com/IDP
* IDP journal: www.landes.com/IDP
* database of experimentally validated IDPs [http://www.disprot.org/]
* database of experimentally validated IDPs [http://www.disprot.org/]
* IDP ensemble database [http://pedb.vib.be/ <ref>{{cite pmid|24174539}}</ref>]
* IDP ensemble database [http://pedb.vib.be/<ref>{{cite pmid|24174539}}</ref>]


== References ==
== References ==
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[[:Category:Biochemistry]]
[[:Category:Biochemistry]]
[[:Category:Structural biology]]
[[:Category:Structural biology]]

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Revision as of 21:21, 10 March 2014

  • Comment: You need to write paragraphs of prose - not bulleted lists - that explain what this is all about. Lists of people without explanations what each of them have to do with the topic are meaningless. Write an article not a "powerpoint presentation". By the way - a "See also" list is only supposed to contain links to other relevant articles here on the English Wikipedia. I have requested WP:WikiProject Molecular and Cellular Biology members to take a look here and assist you with this article. Roger (Dodger67) (talk) 18:45, 10 March 2014 (UTC)
  • Comment: No references provided, just a listing of people, without understanding how they relate to the IDP. Not in the form of an article but several disjointed lists. See WP:REFB for referencing basics. The Ukulele Dude - Aggie80 (talk) 14:20, 9 March 2014 (UTC)

Intrinsically Disordered Protein (IDP)

Protein function was originially thought to depend on a fixed threedimensional (3D) structure. This dogm has been challenged over the last decades by exponentially increasing evidence from various branches of structural biology as briefly outlined below. Next to ordered proteins, so-called Intrinsically Disordered Proteins (IDPs) are a very large and functionally important class of proteins.

History and background

>Levinthal's paradox(1969): The systematic conformational search of a long polypeptide is unlikely to yield folded protein on biologically relevant timescales (i.e. within seconds to minutes).

>Anfinsen's Dogma (1973): (some) small proteins can fold spontaneously.[1] >x-ray crystallographic evidence (1950s-now): large protein regions cannot be assigned in the electron density maps, which suggests that they are not fixed at unique positions relative to the crystal lattice or in other words that they are "disordered".

>NMR datasets: large flexible linkers and termini in many solved structural ensembles.

>large (at least transiently) intrinsically unstructured protein regions are functional in vitro.

>bioinformatic predictions of intrinsic disorder in proteins (~2001): intrinsic disorder is more common in sequenced/predicted proteomes than in the latest PDB update.[2] >IDPs are highly abundant among disease-related proteins: birth of the D2 concept (2008).[3]

Definition

Intrinsically disordered proteins are defined by the lack of a fixed ("ordered") 3D structure[4].

In other words all proteins, which are not intrinsically ordered are intrinsically disordered. IDPs cover a very large spectrum from fully unstructured to almost completely folded structures: random coils, (pre-)molten globules, well-folded multi-domain proteins connected by large linkers.

Bioinformatic analysis

Most algorithms predict Intrinsic Disorder (ID) propensity List_of_disorder_prediction_software with high accuracy (approaching around 80%) based on

  • primary sequence composition
  • similarity to unassigned segments in protein x-ray datasets, flexible regions in NMR studies
  • physico-chemical properties of amino acids

Experimental analysis

Several structural methods exist to characterise IDPs:

  • bulk methods to study IDPs include: SAXS for ensemble shape information, NMR for atomistic ensemble refinement, Fluorescence for visualising molecular interactions and conformational transitions, x-ray crystallography to highlight more mobile regions in otherwise rigid protein crystals, cryo-EM to reveal less fixed parts of proteins, light scattering to monitor size distributions of IDPs or their aggregation kinetics, Circular Dichroism to monitor secondary structure of IDPs,..
  • single-molecule methods to study IDPs include: spFRET[5] to study conformational flexibilty of IDPs and the kinetics of structural transitions, optical tweezers[6] for high-resolution insights into the ensembles of IDPs and their oligomers or aggregates, nanopores[7] to unveal global shape distributions of IDPs, magnetic tweezers[8] to study structural transitions for long times at low forces, high-speed AFM [9] to visualise the spatiotemporal flexibility of IDPs directly.

Pioneering IDP labs

  • Experimental and computational labs focusing on IDPs:
    • Keith Dunker (coined the term IDP, recognised IDPs as distinc class of proteins with important biological functions, established many prediction algorithms to characterise IDPs in thousands proteomes), [10]
    • Peter Tompa (contributed early studies of oversized IDPs and disordered plant chaperones) [11]
    • Vladimir Uversky (pioneer in theoretical and experimental biophysics of IDPs) [12]
    • Madan Babu (pioneer in IDPs in transcription control) [13]
    • Jim Bardwell (pioneer in discovery of intrinsically disordered molecular chaperones) [14]
    • Ursula Jakob (pioneer in conditional disorder and its role for molecular chaperoning) [15]
    • Philipp Selenko (pioneer in in-cell characterisation of IDPs) [16]
    • Michael Woodside (pioneer in optical tweezers studies on aggregation) [17]
    • Madelon Maurice (pioneer in IDP scaffolds in Wnt signalling) [18]
    • Sir Alan Fersht (pioneer in structural studies on the most frequently cancer-mutated IDP, p53) [19]
    • Stefan Rudiger (pioneer in Hsp90-associated IDP recognition mechanisms) [20]
    • Tobias Madl (pioneer in SAXS-NMR protein complex determination methodology development) [21]
    • Yongli Zhang (pioneer in IDP unfolding) [22]
    • Peter Wright (pioneer in mechanistic analysis of coupled folding and binding of IDPs) [23]
    • Jane Dyson (pioneer in NMR studies on various biologically important IDPs) [24]
    • Rohit Pappu (pioneer in modelling of electrostatic malleability of IDP ensembles) [25]
    • Inke Nathke (pioneer in research on APC, one of the largest IDPs) [26]
    • Richard Kriwacki (pioneer in structural studies on binding-induced folding of IDPs) [27]
    • Benjamin Schuler (pioneer in single-molecule fluorescence studies on IDPs) [28]
    • Ashok Deniz (pioneer in single-molecule fluorescence studies on IDPs) [29]
    • David Klenerman (pioneer in single-molecule fluorescence studies on IDPs) [30]

See also

Intrinsically_unstructured_proteins [1]

  • IDP journal: www.landes.com/IDP
  • database of experimentally validated IDPs [2]
  • IDP ensemble database [31]

References

  1. ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 4124164, please use {{cite journal}} with |pmid=4124164 instead.
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Category:Molecular biology techniques Category:Proteomics Category:Biophysics Category:Biochemistry Category:Structural biology

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