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The Protein Ensemble Database

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Book cover Intrinsically Disordered Proteins Studied by NMR Spectroscopy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 870))

Abstract

The scientific community’s major conceptual notion of structural biology has recently shifted in emphasis from the classical structure-function paradigm due to the emergence of intrinsically disordered proteins (IDPs). As opposed to their folded cousins, these proteins are defined by the lack of a stable 3D fold and a high degree of inherent structural heterogeneity that is closely tied to their function. Due to their flexible nature, solution techniques such as small-angle X-ray scattering (SAXS), nuclear magnetic resonance (NMR) spectroscopy and fluorescence resonance energy transfer (FRET) are particularly well-suited for characterizing their biophysical properties. Computationally derived structural ensembles based on such experimental measurements provide models of the conformational sampling displayed by these proteins, and they may offer valuable insights into the functional consequences of inherent flexibility. The Protein Ensemble Database (http://pedb.vib.be) is the first openly accessible, manually curated online resource storing the ensemble models, protocols used during the calculation procedure, and underlying primary experimental data derived from SAXS and/or NMR measurements. By making this previously inaccessible data freely available to researchers, this novel resource is expected to promote the development of more advanced modelling methodologies, facilitate the design of standardized calculation protocols, and consequently lead to a better understanding of how function arises from the disordered state.

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References

  • Allison JR, Varnai P, Dobson CM et al (2009) Determination of the free energy landscape of α-synuclein using spin label nuclear magnetic resonance measurements. J Am Chem Soc 131(51):18314–18326. doi:10.1021/ja904716h

    Article  CAS  PubMed  Google Scholar 

  • Benson DA, Cavanaugh M, Clark K et al (2013) GenBank. Nucleic Acids Res 41(Database issue):D36–D42. doi:10.1093/nar/gks1195

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Berman HM, Westbrook J, Feng Z et al (2000) The protein data bank. Nucleic Acids Res 28(1):235–242

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Bernadό P, Svergun DI (2012) Structural analysis of intrinsically disordered proteins by small-angle X-ray scattering. Mol Biosyst 8(1):151–167. doi:10.1039/c1mb05275f

    Article  CAS  PubMed  Google Scholar 

  • Bernadό P, Mylonas E, Petoukhov MV et al (2007) Structural characterization of flexible proteins using small-angle X-ray scattering. J Am Chem Soc 129(17):5656–5664. doi:10.1021/ja069124n

    Article  CAS  PubMed  Google Scholar 

  • Canutescu AA, Shelenkov AA, Dunbrack RL Jr (2003) A graph-theory algorithm for rapid protein side-chain prediction. Protein Sci (A publication of the Protein Society) 12(9):2001–2014. doi:10.1110/ps.03154503

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cavalli A, Camilloni C, Vendruscolo M (2013) Molecular dynamics simulations with replica-averaged structural restraints generate structural ensembles according to the maximum entropy principle. Journal Chem Phys 138(9):094112. doi:10.1063/1.4793625

    Article  Google Scholar 

  • Chiti F, Dobson CM (2006) Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366. doi:10.1146/annurev.biochem.75.101304.123901

    Article  CAS  PubMed  Google Scholar 

  • Daughdrill GW, Kashtanov S, Stancik A et al (2012) Understanding the structural ensembles of a highly extended disordered protein. Mol Biosyst 8(1):308–319. doi:10.1039/c1mb05243h

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dunker AK, Silman I, Uversky VN et al (2008) Function and structure of inherently disordered proteins. Curr Opin Struct Biol 18(6):756–764. doi:10.1016/j.sbi.2008.10.002

    Article  CAS  PubMed  Google Scholar 

  • Dyson HJ, Wright PE (2005) Intrinsically unstructured proteins and their functions. Nat Rev Mol Cell Biol 6(3):197–208. doi:10.1038/nrm1589

    Article  CAS  PubMed  Google Scholar 

  • Eyal E, Najmanovich R, McConkey BJ et al (2004) Importance of solvent accessibility and contact surfaces in modeling side-chain conformations in proteins. J Comput Chem 25(5):712–724. doi:10.1002/jcc.10420

    Article  CAS  PubMed  Google Scholar 

  • Feldman HJ, Hogue CW (2000) A fast method to sample real protein conformational space. Proteins 39(2):112–131

    Article  CAS  PubMed  Google Scholar 

  • Feldman HJ, Hogue CW (2002) Probabilistic sampling of protein conformations: new hope for brute force? Proteins 46(1):8–23

    Article  CAS  PubMed  Google Scholar 

  • Fisher CK, Stultz CM (2011) Constructing ensembles for intrinsically disordered proteins. Curr Opin Struct Biol 21(3):426–431. doi:10.1016/j.sbi.2011.04.001

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Gsponer J, Babu MM (2009) The rules of disorder or why disorder rules. Prog Biophys Mol Biol 99(2/3):94–103. doi:10.1016/j.pbiomolbio.2009.03.001

    Article  CAS  PubMed  Google Scholar 

  • Huang JR, Grzesiek S (2010) Ensemble calculations of unstructured proteins constrained by RDC and PRE data: a case study of urea-denatured ubiquitin. J Am Chem Soc 132(2):694–705. doi:10.1021/ja907974m

    Article  CAS  PubMed  Google Scholar 

  • Jensen MR, Communie G, Ribeiro EA Jr et al (2011) Intrinsic disorder in measles virus nucleocapsids. Proc Natl Acad Sci U S A 108(24):9839–9844. doi:10.1073/pnas.1103270108

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jensen MR, Ruigrok RW, Blackledge M (2013) Describing intrinsically disordered proteins at atomic resolution by NMR. Curr Opin Struct Biol 23(3):426–435. doi:10.1016/j.sbi.2013.02.007

    Article  CAS  PubMed  Google Scholar 

  • Krzeminski M, Marsh JA, Neale C et al (2013) Characterization of disordered proteins with ENSEMBLE. Bioinformatics 29(3):398–399. doi:10.1093/bioinformatics/bts701

    Article  CAS  PubMed  Google Scholar 

  • Marsh JA, Forman-Kay JD (2011) Ensemble modeling of protein disordered states: experimental restraint contributions and validation. Proteins. doi:10.1002/prot.23220

    Google Scholar 

  • Mertens HD, Piljic A, Schultz C et al (2012) Conformational analysis of a genetically encoded FRET biosensor by SAXS. Biophys J 102(12):2866–2875. doi:10.1016/j.bpj.2012.05.009

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Mittag T, Marsh J, Grishaev A et al (2010) Structure/function implications in a dynamic complex of the intrinsically disordered Sic1 with the Cdc4 subunit of an SCF ubiquitin ligase. Structure 18(4):494–506. doi:10.1016/j.str.2010.01.020

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ozenne V, Bauer F, Salmon L et al (2012) Flexible-meccano: a tool for the generation of explicit ensemble descriptions of intrinsically disordered proteins and their associated experimental observables. Bioinformatics 28(11):1463–1470. doi:10.1093/bioinformatics/bts172

    Article  CAS  PubMed  Google Scholar 

  • Salmon L, Nodet G, Ozenne V et al (2010) NMR characterization of long-range order in intrinsically disordered proteins. J Am Chem Soc 132(24):8407–8418. doi:10.1021/ja101645g

    Article  CAS  PubMed  Google Scholar 

  • Schneider R, Huang JR, Yao M et al (2012) Towards a robust description of intrinsic protein disorder using nuclear magnetic resonance spectroscopy. Mol Biosyst 8(1):58–68. doi:10.1039/c1mb05291h

    Article  CAS  PubMed  Google Scholar 

  • Sethi A, Anunciado D, Tian J et al (2013) Deducing conformational variability of intrinsically disordered proteins from infrared spectroscopy with Bayesian statistics. Chem Phys 422. doi:10.1016/j.chemphys.2013.05.005

    Google Scholar 

  • Shen Y, Bax A (2007) Protein backbone chemical shifts predicted from searching a database for torsion angle and sequence homology. J Biomol NMR 38(4):289–302. doi:10.1007/s10858-007-9166-6

    Article  CAS  PubMed  Google Scholar 

  • Sickmeier M, Hamilton JA, LeGall T et al (2007) DisProt: the database of disordered proteins. Nucleic Acids Res 35(Database issue):D786–D793. doi:10.1093/nar/gkl893

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tompa P (2002) Intrinsically unstructured proteins. Trends Biochem Sci 27(10):527–533

    Article  CAS  PubMed  Google Scholar 

  • Tompa P (2011) Unstructural biology coming of age. Curr Opin Struct Biol 21(3):419–425. doi:10.1016/j.sbi.2011.03.012. (S0959-440X(11)00064-9 [pii])

    Article  CAS  PubMed  Google Scholar 

  • Tompa P, Fuxreiter M (2008) Fuzzy complexes: polymorphism and structural disorder in protein-protein interactions. Trends Biochem Sci 33(1):2–8. doi:10.1016/j.tibs.2007.10.003

    Article  CAS  PubMed  Google Scholar 

  • Tompa P, Varadi M (2014) Predicting the predictive power of IDP ensembles. Structure 22(2):177–178. doi:10.1016/j.str.2014.01.003

    Article  CAS  PubMed  Google Scholar 

  • Ulrich EL, Akutsu H, Doreleijers JF et al (2008) BioMagResBank. Nucleic Acids Res 36(Database issue):D402–D408. doi:10.1093/nar/gkm957

    PubMed Central  CAS  PubMed  Google Scholar 

  • UniProt C (2014) Activities at the universal protein resource (UniProt). Nucleic Acids Res 42(Database issue):D191–D198. doi:10.1093/nar/gkt1140

    Google Scholar 

  • Uversky VN, Gillespie JR, Fink AL (2000) Why are “natively unfolded” proteins unstructured under physiologic conditions? Proteins 41(3):415–427

    Article  CAS  PubMed  Google Scholar 

  • Varadi M, Kosol S, Lebrun P et al (2014) pE-DB: a database of structural ensembles of intrinsically disordered and of unfolded proteins. Nucleic Acids Res 42(Database issue):D326–D335. doi:10.1093/nar/gkt960

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wu KP, Weinstock DS, Narayanan C et al (2009) Structural reorganization of α-synuclein at low pH observed by NMR and REMD simulations. J Mol Biol 391(4):784–796. doi:10.1016/j.jmb.2009.06.063

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Structural Biology, Vlaams Institute voor Biotechnologie (VIB), Brussels, Belgium

    Mihaly Varadi & Peter Tompa

  2. Vrije Universiteit Brussel (VUB), Structural Biology Brussel (SBB), Brussels, Belgium

    Mihaly Varadi & Peter Tompa

  3. Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary

    Peter Tompa

Authors
  1. Mihaly Varadi
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  2. Peter Tompa
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Correspondence to Peter Tompa .

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Editors and Affiliations

  1. CERM and Department of Chemistry, "Ugo Schiff" University of Florence, Florence, Italy

    Isabella C. Felli

  2. CERM and Department of Chemistry, "Ugo Schiff" University of Florence, Florence, Italy

    Roberta Pierattelli

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Varadi, M., Tompa, P. (2015). The Protein Ensemble Database. In: Felli, I., Pierattelli, R. (eds) Intrinsically Disordered Proteins Studied by NMR Spectroscopy. Advances in Experimental Medicine and Biology, vol 870. Springer, Cham. https://doi.org/10.1007/978-3-319-20164-1_11

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