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* [[Molten globule]]
* [[Molten globule]]
* [[Random coil]]
* [[Random coil]]
== Pioneering IDP research labs ==

* Experimental and computational labs focusing on IDPs (very incomplete list as of now;):
**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.<ref>{{cite web|url=http://www.compbio.iupui.edu/group/5/pages/about_us |title=About Us - Keith Dunker Lab - Center for Computational Biology and Bioinformatics |publisher=Compbio.iupui.edu |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|11381529}}</ref>
**Peter Tompa contributed early studies of oversized IDPs and disordered plant chaperones.<ref>{{cite web|url=http://www.vib.be/en/research/scientists/Pages/Peter-Tompa-Lab.aspx |title=Peter Tompa Lab |publisher=Vib.be |date=2011-05-11 |accessdate=2014-03-11}}</ref><ref>{{cite pmid|12368089}}</ref>
**Vladimir Uversky is a pioneer in theoretical and experimental biophysics of IDPs.<ref>https://hsccf.hsc.usf.edu/facultyDirectory/researchDirectory/search_profile.cfm?person_id=2838234</ref><ref>{{cite pmid|11025552}}</ref>
**Madan Babu is a pioneer in IDPs in transcription control.<ref>{{cite web|url=http://mbgroup.mrc-lmb.cam.ac.uk/research/ |title=Research &#124; M. Madan Babu's Lab |publisher=Mbgroup.mrc-lmb.cam.ac.uk |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|19039133}}</ref>
**Jim Bardwell is a pioneer in the discovery of intrinsically disordered molecular chaperones.<ref>{{cite web|url=http://labs.mcdb.lsa.umich.edu/labs/bardwell/ |title=The Bardwell Lab the University of Michigan |publisher=Labs.mcdb.lsa.umich.edu |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|23018052}}</ref>
**Ursula Jakob is a pioneer in conditional disorder and its role for molecular chaperoning.<ref>{{cite web|url=http://www.biochem.med.umich.edu/?q=jakob |title=Ursula Jakob, Ph.D. &#124; University of Michigan Department of Biological Chemistry |publisher=Biochem.med.umich.edu |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|23018052}}</ref>
**Philipp Selenko is a pioneer in in-cell characterisation of IDPs.<ref>{{cite web|url=http://www.incellnmr.net/ |title=Welcome to the Selenko Lab |publisher=In-cell NMR |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|22988846}}</ref>
**Michael Woodside pioneered optical tweezers studies on aggregation.<ref>{{cite web|url=http://www.ualberta.ca/~mwoodsid/Home.html |title=Woodside Lab |publisher=Ualberta.ca |date=2012-08-22 |accessdate=2014-03-11}}</ref><ref>{{cite pmid|22421432}}</ref>
**Madelon Maurice is a pioneer in IDP scaffolds in Wnt signalling.<ref>{{cite web|url=http://www.cellbiology-utrecht.nl/research/maurice.html |title=Maurice - Cell Biology UMC Utrecht |publisher=Cellbiology-utrecht.nl |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|21859464}}</ref>
**Sir [[Alan Fersht]] pioneered structural studies on the most frequently cancer-mutated IDP, p53.<ref>{{cite web|author=UK |url=http://www2.mrc-lmb.cam.ac.uk/group-leaders/a-to-g/alan-fersht/ |title=Alan Fersht &#124; MRC Laboratory of Molecular Biology |publisher=.mrc-lmb.cam.ac.uk |date=2013-11-21 |accessdate=2014-03-11}}</ref><ref>{{cite pmid|22988846}}</ref>
**Stefan Rudiger is a pioneer in Hsp90-associated IDP recognition mechanisms.<ref>{{cite web|url=http://www.uu.nl/medewerkers/SGDRudiger1/0 |title=dr. S.G.D. (Stefan) Rüdiger - Betawetenschappen - Universiteit Utrecht |publisher=Uu.nl |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|24581495}}</ref>
**Tobias Madl pioneered SAXS-NMR protein complex determination methodology development.<ref>{{cite web|url=http://www.madllab.ch.tum.de/ |title=Emmy-Noether Nachwuchsgruppe: Startseite |publisher=Madllab.ch.tum.de |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|21753750}}</ref>
**Yongli Zhang is a pioneer in IDP unfolding.<ref>{{cite web|url=http://bbs.yale.edu/people/yongli_zhang.profile |title=Yongli Zhang, PhD > Biological & Biomedical Sciences &#124; Yale University |publisher=Bbs.yale.edu |date=2012-12-12 |accessdate=2014-03-11}}</ref><ref>{{cite pmid|22903523}}</ref>
**Peter Wright pioneered the mechanistic analysis of coupled folding and binding of IDPs.<ref>{{cite web|url=http://www.scripps.edu/wright/ |title=Peter Wright |publisher=Scripps.edu |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|11823864}}</ref>
**Jane Dyson is a pioneer in NMR studies on various biologically important IDPs.<ref>{{cite web|url=http://www.scripps.edu/dyson/ |title=Jane Dyson |publisher=Scripps.edu |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|21729349}}</ref>
**Rohit Pappu pioneered modelling of electrostatic malleability of IDP ensembles.<ref>{{cite web|author=Alex Holehouse |url=http://pappulab.wustl.edu/ |title=Pappu Lab |publisher=Pappulab.wustl.edu |date=2014-02-11 |accessdate=2014-03-11}}</ref><ref>{{cite pmid|23901099}}</ref>
**Inke Nathke pioneered research on APC, one of the largest IDPs.<ref>{{cite web|url=http://www.lifesci.dundee.ac.uk/groups/inke_nathke/ |title=Inke Nathke &#124; |publisher=Lifesci.dundee.ac.uk |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|23589686}}</ref>
**Richard Kriwacki pioneered structural studies on binding-induced folding of IDPs.<ref>{{cite web|url=http://www.stjuderesearch.org/site/lab/kriwacki |title=Kriwacki laboratory |publisher=St. Jude Research |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|21358637}}</ref>
**Benjamin Schuler pioneered single-molecule fluorescence studies on IDPs.<ref>{{cite web|url=http://www.bioc.uzh.ch/schuler/ |title=Ben Schuler research group |publisher=Bioc.uzh.ch |date=2013-10-31 |accessdate=2014-03-11}}</ref><ref>{{cite pmid|24432838}}</ref>
**Ashok Deniz pioneered single-molecule fluorescence studies on IDPs.<ref>{{cite web|url=http://www.scripps.edu/deniz/ |title=The Deniz Lab |publisher=Scripps.edu |date=2014-01-23 |accessdate=2014-03-11}}</ref><ref>{{cite pmid|23783631}}</ref>
**David Klenerman pioneered single-molecule fluorescence studies on IDPs.<ref>{{cite web|url=http://www.ch.cam.ac.uk/person/dk10012 |title=Klenerman &#124; Department of Chemistry |publisher=Ch.cam.ac.uk |date= |accessdate=2014-03-11}}</ref><ref>{{cite pmid|22632969}}</ref>


== References ==
== References ==

Version vom 27. März 2014, 23:09 Uhr

An ensemble of NMR structures of the Thylakoid soluble phosphoprotein TSP9, which shows a largely flexible protein chain.[1]

An intrinsically disordered protein (IDP) is a protein that lacks a fixed or ordered three-dimensional structure.[2][3][4] IDPs cover a spectrum of states from fully unstructured to partially structured and include random coils, (pre-)molten globules, and large multi-domain proteins connected by flexible linkers.

The discovery of IDPs has challenged the traditional protein structure paradigm, that protein function depends on a fixed three-dimensional structure. This dogma has been challenged over the last decades increasing evidence from various branches of structural biology. Despite their lack of stable structure, IDPs are a very large and functionally important class of proteins. In some cases, IDPs can adopt a fixed three-dimensional structure after binding to other macromolecules.

History

In the 1930s -1950s, the first protein structures were solved by protein crystallography. These early structures suggested that a fixed three-dimensional structure might be generally required to mediate biological functions of proteins. Already in the 1960s, Levinthal's paradox suggested that the systematic conformational search of a long polypeptide is unlikely to yield a single folded protein structure on biologically relevant timescales (i.e. seconds to minutes). Curiously, for many (small) proteins or protein domains, relatively rapid and efficient refolding can be observed in vitro. As stated in Anfinsen's Dogma (1973), the fixed 3D structure of these proteins is uniquely encoded in its primary structure (=amino acid sequence), is kinetically accessible and stable under a range of (near)physiological conditions and can therefore be considered as the native state of such "ordered" proteins.

During the subsequent decades, however, many large protein regions could not be assigned in x-ray datasets, indicating that they occupy multiple positions which average out in electron density maps. The lack of a fixed, unique positions relative to the crystal lattice suggested that these regions were "disordered". Additional techniques for determining protein structures, such as NMR, demonstrated the presence of large flexible linkers and termini in many solved structural ensembles. It is now generally accepted that proteins exist as an ensemble of similar structures with some regions more constrained than others. Intrinsically Unstructured Proteinss (IUPs) occupy the extreme end of this spectrum of flexibility, whereas IDPs also include proteins of considerable local structure tendency or flexible multidomain assemblies.

These disordered regions have subsequently been shown to have important functions both ''in vitro'' and ''in vivo''. In the 2000s, bioinformatic predictions of intrinsic disorder in proteins indicated that intrinsic disorder is more common in sequenced/predicted proteomes than in known structures in the protein database.[2] In the 2010s it became clear that IDPs are highly abundant among disease-related proteins.[5]

Biological roles of intrinsic disorder

Many disordered proteins have the binding affinity with their receptors regulated by post-translational modification, thus it has been proposed that the flexibility of disordered proteins facilitates the different conformational requirements for binding the modifying enzymes as well as their receptors.[6] Intrinsic disorder is particularly enriched in proteins implicated in cell signaling, transcription and chromatin remodeling functions.[7][8]

Flexible linkers

Disordered regions are often found as flexible linkers (or loops) connecting two globular or transmembrane domains. Linker sequences vary greatly in length and amino acid sequence, but are similar in amino acid composition (rich in polar uncharged amino acids). Flexible linkers allow the connecting domains to freely twist and rotate through space to recruit their binding partners or for those binding partners to induce larger scale interdomain conformation changes.

Coupled folding and binding

Many unstructured proteins undergo transitions to more ordered states upon binding to their targets. The coupled folding and binding may be local, involving only a few interacting residues, or it might involve an entire protein domain. It was recently shown that the coupled folding and binding allows the burial of a large surface area that would be possible only for fully structured proteins if they were much larger.[9] Moreover, certain disordered regions might serve as "molecular switches" in regulating certain biological function by switching to ordered conformation upon molecular recognition like small molecule-binding, DNA/RNA binding, ion interactions etc.[10]

The ability of disordered proteins to bind, and thus to exert a function, shows that stability is not a required condition. Many short functional sites, for example Short Linear Motifs are over-represented in disordered proteins.

Disorder in the bound state (Fuzzy complexes)

Intrinsically disordered proteins can retain their conformational freedom even when they bind specifically to other proteins. The structural disorder in bound state can be static or dynamic. In fuzzy complexes structural multiplicity is required for function and the manipulation of the bound disordered region changes activity. The conformational ensemble of the complex is modulated via post-translational modifications or protein interactions.[11] Specificity of DNA binding proteins often depends on the length of fuzzy regions, which is varied by alternative splicing.[12]

Disorder identification and analysis

Disorder prediction software

Disorder prediction algorithms can predict Intrinsic Disorder (ID) propensity 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 and physico-chemical properties of amino acids.

Intrinsically unstructured proteins are characterized by a low content of bulky hydrophobic amino acids and a high proportion of polar and charged amino acids. Thus disordered sequences cannot bury sufficient hydrophobic core to fold like stable globular proteins. In some cases, hydrophobic clusters in disordered sequences provide the clues for identifying the regions that undergo coupled folding and binding. Such signatures are the basis of the prediction methods below.

Many disordered proteins also reveal low complexity sequences, i.e. sequences with over-representation of a few residues. While low complexity sequences are a strong indication of disorder, the reverse is not necessarily true, that is, not all disordered proteins have low complexity sequences. Disordered proteins have a low content of predicted secondary structure. There are many computational methods that exploit sequence information to predict whether a protein is disordered.[13] Notable examples of such software include IUPRED, TISS [14] and Disopred. Different software may use different definitions of disorder. Since the methods above use different definitions of disorder and they were trained on different datasets, it is difficult to estimate their relative accuracy. Disorder prediction category is a part of biannual CASP experiment that is designed to test methods according accuracy in finding regions with missing 3D structure (marked in PDB files as REMARK465). Various protocols and methodologies of analysis of IDP's such as studies based on quantitative analysis of GC content in genes and their respective chromosomal bands to understand functionally Intrinsically disordered protein segments.[15][16]

Experimental validation

Intrinsically unfolded proteins, once purified, can be identified by various experimental methods. The primary method to obtain information on disordered regions of a protein is NMR spectroscopy. The lack of electron density in X-ray crystallographic studies may also be a sign of disorder.

Folded proteins have a high density (partial specific volume of 0.72-0.74 mL/g) and commensurately small radius of gyration. Hence, unfolded proteins can be detected by methods that are sensitive to molecular size, density or hydrodynamic drag, such as size exclusion chromatography, analytical ultracentrifugation, Small angle X-ray scattering (SAXS), and measurements of the diffusion constant. Unfolded proteins are also characterized by their lack of secondary structure, as assessed by far-UV (170-250 nm) circular dichroism (esp. a pronounced minimum at ~200 nm) or infrared spectroscopy. Unfolded proteins also have exposed backbone peptide groups exposed to solvent, so that they are readily cleaved by proteases, undergo rapid hydrogen-deuterium exchange and exhibit a small dispersion (<1 ppm) in their 1H amide chemical shifts as measured by NMR. (Folded proteins typically show dispersions as large as 5 ppm for the amide protons.) Recently, new methods including Fast parallel proteolysis (FASTpp) have been introduced, which allow to determine the fraction folded/disordered without the need for purification.[17][18]

Bulk methods to study IDP structure and dynamics 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[19] to study conformational flexibilty of IDPs and the kinetics of structural transitions, optical tweezers[20] for high-resolution insights into the ensembles of IDPs and their oligomers or aggregates, nanopores[21] to reveal global shape distributions of IDPs, magnetic tweezers[22] to study structural transitions for long times at low forces, high-speed AFM [23] to visualise the spatio-temporal flexibility of IDPs directly.

Disorder and disease

Intrinsically unstructured proteins have been implicated in a number of diseases.[24] Aggregation of misfolded proteins is the cause of many synucleinopathies. The aggregation of the intrinsically unstructured protein α-Synuclein is thought to be responsible. The structural flexibility of this protein together with its susceptibility to modification in the cell leads to misfolding and aggregation. Genetics, oxidative and nitrative stress as well as mitochondrial impairment impact the structural flexibility of the unstructured α-Synuclein protein and associated disease mechanisms.[25] Many key oncogenes have large intrinsically unstructured regions, for example p53 and BRCA1. These regions of the proteins are responsible for mediating many of their interactions.

Computer Simulations

Structural and dynamical properties of intrinsically unstructured proteins are being studied by molecular dynamics simulations.[26][27][28] Findings from these simulations suggest a highly flexible conformational ensemble of intrinsically disordered proteins at different temperatures which is related to the presence of low free energy barriers.

Effects of confinement have been also recently addressed.[29] These studies suggest that confinement tends to increase the population of turn structures with respect to the population of coils and β-hairpins for instance.

See also

Pioneering IDP research labs

  • Experimental and computational labs focusing on IDPs (very incomplete list as of now;):
    • 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.[30][31]
    • Peter Tompa contributed early studies of oversized IDPs and disordered plant chaperones.[32][33]
    • Vladimir Uversky is a pioneer in theoretical and experimental biophysics of IDPs.[34][35]
    • Madan Babu is a pioneer in IDPs in transcription control.[36][37]
    • Jim Bardwell is a pioneer in the discovery of intrinsically disordered molecular chaperones.[38][39]
    • Ursula Jakob is a pioneer in conditional disorder and its role for molecular chaperoning.[40][41]
    • Philipp Selenko is a pioneer in in-cell characterisation of IDPs.[42][43]
    • Michael Woodside pioneered optical tweezers studies on aggregation.[44][45]
    • Madelon Maurice is a pioneer in IDP scaffolds in Wnt signalling.[46][47]
    • Sir Alan Fersht pioneered structural studies on the most frequently cancer-mutated IDP, p53.[48][49]
    • Stefan Rudiger is a pioneer in Hsp90-associated IDP recognition mechanisms.[50][51]
    • Tobias Madl pioneered SAXS-NMR protein complex determination methodology development.[52][53]
    • Yongli Zhang is a pioneer in IDP unfolding.[54][55]
    • Peter Wright pioneered the mechanistic analysis of coupled folding and binding of IDPs.[56][57]
    • Jane Dyson is a pioneer in NMR studies on various biologically important IDPs.[58][59]
    • Rohit Pappu pioneered modelling of electrostatic malleability of IDP ensembles.[60][61]
    • Inke Nathke pioneered research on APC, one of the largest IDPs.[62][63]
    • Richard Kriwacki pioneered structural studies on binding-induced folding of IDPs.[64][65]
    • Benjamin Schuler pioneered single-molecule fluorescence studies on IDPs.[66][67]
    • Ashok Deniz pioneered single-molecule fluorescence studies on IDPs.[68][69]
    • David Klenerman pioneered single-molecule fluorescence studies on IDPs.[70][71]

References

Vorlage:Reflist

External Links

  1. ↑ Song J, Lee MS, Carlberg I, Vener AV, Markley JL: Micelle-induced folding of spinach thylakoid soluble phosphoprotein of 9 kDa and its functional implications. In: Biochemistry. 45. Jahrgang, Nr. 51, Dezember 2006, S. 15633–43, doi:10.1021/bi062148m, PMID 17176085, PMC 2533273 (freier Volltext).
  2. ↑ a b Vorlage:Cite pmid
  3. ↑ Dyson HJ, Wright PE: Intrinsically unstructured proteins and their functions. In: Nat. Rev. Mol. Cell Biol. 6. Jahrgang, Nr. 3, März 2005, S. 197–208, doi:10.1038/nrm1589, PMID 15738986.
  4. ↑ Dunker AK, Silman I, Uversky VN, Sussman JL: Function and structure of inherently disordered proteins. In: Curr. Opin. Struct. Biol. 18. Jahrgang, Nr. 6, Dezember 2008, S. 756–64, doi:10.1016/j.sbi.2008.10.002, PMID 18952168.
  5. ↑ Vorlage:Cite pmid
  6. ↑ Collins MO, Yu L, Campuzano I, Grant SG, Choudhary JS: Phosphoproteomic analysis of the mouse brain cytosol reveals a predominance of protein phosphorylation in regions of intrinsic sequence disorder. In: Mol. Cell Proteomics. 7. Jahrgang, Nr. 7, Juli 2008, S. 1331–48, doi:10.1074/mcp.M700564-MCP200, PMID 18388127.
  7. ↑ Iakoucheva LM, Brown CJ, Lawson JD, Obradović Z, Dunker AK: Intrinsic disorder in cell-signaling and cancer-associated proteins. In: J. Mol. Biol. 323. Jahrgang, Nr. 3, Oktober 2002, S. 573–84, doi:10.1016/S0022-2836(02)00969-5, PMID 12381310.
  8. ↑ Sandhu KS: Intrinsic disorder explains diverse nuclear roles of chromatin remodeling proteins. In: J. Mol. Recognit. 22. Jahrgang, Nr. 1, 2009, S. 1–8, doi:10.1002/jmr.915, PMID 18802931.
  9. ↑ Gunasekaran K, Tsai CJ, Kumar S, Zanuy D, Nussinov R: Extended disordered proteins: targeting function with less scaffold. In: Trends Biochem. Sci. 28. Jahrgang, Nr. 2, Februar 2003, S. 81–5, doi:10.1016/S0968-0004(03)00003-3, PMID 12575995.
  10. ↑ Sandhu KS, Dash D: Dynamic alpha-helices: conformations that do not conform. In: Proteins. 68. Jahrgang, Nr. 1, Juli 2007, S. 109–22, doi:10.1002/prot.21328, PMID 17407165.
  11. ↑ M Fuxreiter: Fuzziness: Linking regulation to protein dynamics. In: Molecular bioSystems. 8. Jahrgang, Nr. 1, 2012, S. 168–77, doi:10.1039/c1mb05234a, PMID 21927770.
  12. ↑ M Fuxreiter, I Simon, S Bondos: Dynamic protein-DNA recognition: Beyond what can be seen. In: Trends in biochemical sciences. 36. Jahrgang, Nr. 8, 2011, S. 415–23, doi:10.1016/j.tibs.2011.04.006, PMID 21620710.
  13. ↑ Ferron F, Longhi S, Canard B, Karlin D: A practical overview of protein disorder prediction methods. In: Proteins. 65. Jahrgang, Nr. 1, Oktober 2006, S. 1–14, doi:10.1002/prot.21075, PMID 16856179.
  14. ↑ Coskuner O, Wise-Scira O, Perry G, Kitahara T: The Structures of the E22Δ Mutant-Type Amyloid-β Alloforms and the Impact of E22Δ Mutation on the Structures of the Wild-Type Amyloid-β Alloforms. In: ACS Chemical Neuroscience. 4. Jahrgang, Nr. 2, Oktober 2012, S. 310–320, doi:10.1021/cn300149j.
  15. ↑ Vladimir N Uversky: Digested disorder: Quarterly intrinsic disorder digest (January/February/March, 2013). In: Intrinsically Disordered Proteins. 1. Jahrgang, 2013, S. e25496, doi:10.4161/idp.25496.
  16. ↑ Susan Costantini, Ankush Sharma, Raffaele Raucci, Maria Costantini, Ida Autiero, and Giovanni Colonna: Genealogy of an ancient protein family: the Sirtuins, a family of disordered members. In: BMC evolutionary biology. 13. Jahrgang, März 2013, S. 60, doi:10.1186/1471-2148-13-60, PMID 23497088, PMC 3599600 (freier Volltext).
  17. ↑ David P. Minde, Madelon M. Maurice, Stefan G. D. Rüdiger: Determining Biophysical Protein Stability in Lysates by a Fast Proteolysis Assay, FASTpp. In: PLoS ONE. 7. Jahrgang, Nr. 10, 2012, S. e46147, doi:10.1371/journal.pone.0046147, PMID 23056252, PMC 3463568 (freier Volltext).
  18. ↑ C Park, S Marqusee: Pulse proteolysis: A simple method for quantitative determination of protein stability and ligand binding. In: Nature methods. 2. Jahrgang, Nr. 3, 2005, S. 207–12, doi:10.1038/nmeth740, PMID 15782190.
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  24. ↑ Vladimir N. Uversky, Christopher J. Oldfield, A. Keith Dunker: Intrinsically Disordered Proteins in Human Diseases: Introducing the D2Concept. In: Annual Review of Biophysics. 37. Jahrgang, 2008, S. 215–46, doi:10.1146/annurev.biophys.37.032807.125924, PMID 18573080.
  25. ↑ Orkid Coskuner, Olivia Wise-Scira, Aquila Dunn: Structures of the E46K Mutant-Type α-Synuclein Protein and Impact of E46K Mutation on the Structures of the Wild-Type α-Synuclein Protein. In: ACS Chemical Neuroscience. 4. Jahrgang, 2013, S. 498–508, doi:10.1021/cn3002027.
  26. ↑ Mittal J, Yoo T, Georgiou G, Truskett T: Structural Ensemble of an Intrinsically Disordered Polypeptide. In: J. Of Phys. Chem B. 117. Jahrgang, Dezember 2013, S. 118–124, doi:10.1021/jp308984e.
  27. ↑ Ojeda-May P, Pu J: Replica exchange molecular dynamics simulations of an α/β-type small acid soluble protein (SASP). In: Biophysical Chemistry. 184. Jahrgang, August 2013, S. 17–21, doi:10.1016/j.bpc.2013.07.014, PMID 24029407.
  28. ↑ Higo J, Ito H, Kuroda M, Ono S, Nakajima N, Nakamura H: Energy landscape of a peptide consisting of α-helix, 3-10-helix, β-hairpin, and other disordered conformations. In: Protein Science. 10. Jahrgang, Nr. 6, März 2001, S. 1160–1171, doi:10.1110/ps.44901, PMID 11369854, PMC 2374007 (freier Volltext).
  29. ↑ Rao J, Cruz L: Effects of Confinement on the Structure and Dynamics of an Intrinsically Disordered Peptide: A Molecular-Dynamics Study. In: J. Of Phys. Chem B. 117. Jahrgang, Nr. 14, März 2013, S. 3707–3719, doi:10.1021/jp310623x.
  30. ↑ About Us - Keith Dunker Lab - Center for Computational Biology and Bioinformatics. Compbio.iupui.edu, abgerufen am 11. März 2014.
  31. ↑ Vorlage:Cite pmid
  32. ↑ Peter Tompa Lab. Vib.be, 11. Mai 2011, abgerufen am 11. März 2014.
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  34. ↑ https://hsccf.hsc.usf.edu/facultyDirectory/researchDirectory/search_profile.cfm?person_id=2838234
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  36. ↑ Research | M. Madan Babu's Lab. Mbgroup.mrc-lmb.cam.ac.uk, abgerufen am 11. März 2014.
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  38. ↑ The Bardwell Lab the University of Michigan. Labs.mcdb.lsa.umich.edu, abgerufen am 11. März 2014.
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  40. ↑ Ursula Jakob, Ph.D. | University of Michigan Department of Biological Chemistry. Biochem.med.umich.edu, abgerufen am 11. März 2014.
  41. ↑ Vorlage:Cite pmid
  42. ↑ Welcome to the Selenko Lab. In-cell NMR, abgerufen am 11. März 2014.
  43. ↑ Vorlage:Cite pmid
  44. ↑ Woodside Lab. Ualberta.ca, 22. August 2012, abgerufen am 11. März 2014.
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  46. ↑ Maurice - Cell Biology UMC Utrecht. Cellbiology-utrecht.nl, abgerufen am 11. März 2014.
  47. ↑ Vorlage:Cite pmid
  48. ↑ UK: Alan Fersht | MRC Laboratory of Molecular Biology. .mrc-lmb.cam.ac.uk, 21. November 2013, abgerufen am 11. März 2014.
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  50. ↑ dr. S.G.D. (Stefan) Rüdiger - Betawetenschappen - Universiteit Utrecht. Uu.nl, abgerufen am 11. März 2014.
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  52. ↑ Emmy-Noether Nachwuchsgruppe: Startseite. Madllab.ch.tum.de, abgerufen am 11. März 2014.
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  54. ↑ Yongli Zhang, PhD > Biological & Biomedical Sciences | Yale University. Bbs.yale.edu, 12. Dezember 2012, abgerufen am 11. März 2014.
  55. ↑ Vorlage:Cite pmid
  56. ↑ Peter Wright. Scripps.edu, abgerufen am 11. März 2014.
  57. ↑ Vorlage:Cite pmid
  58. ↑ Jane Dyson. Scripps.edu, abgerufen am 11. März 2014.
  59. ↑ Vorlage:Cite pmid
  60. ↑ Alex Holehouse: Pappu Lab. Pappulab.wustl.edu, 11. Februar 2014, abgerufen am 11. März 2014.
  61. ↑ Vorlage:Cite pmid
  62. ↑ Inke Nathke |. Lifesci.dundee.ac.uk, abgerufen am 11. März 2014.
  63. ↑ Vorlage:Cite pmid
  64. ↑ Kriwacki laboratory. St. Jude Research, abgerufen am 11. März 2014.
  65. ↑ Vorlage:Cite pmid
  66. ↑ Ben Schuler research group. Bioc.uzh.ch, 31. Oktober 2013, abgerufen am 11. März 2014.
  67. ↑ Vorlage:Cite pmid
  68. ↑ The Deniz Lab. Scripps.edu, 23. Januar 2014, abgerufen am 11. März 2014.
  69. ↑ Vorlage:Cite pmid
  70. ↑ Klenerman | Department of Chemistry. Ch.cam.ac.uk, abgerufen am 11. März 2014.
  71. ↑ Vorlage:Cite pmid
Abgerufen von „https://de.wikipedia.org/w/index.php?title=Intrinsisch_ungeordnete_Proteine&oldid=166100411“