Journal ArticleDOI
Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm.
Peter E. Wright,H. Jane Dyson +1 more
TLDR
Many proteins that lack intrinsic globular structure under physiological conditions have now been recognized, and it appears likely that their rapid turnover, aided by their unstructured nature in the unbound state, provides a level of control that allows rapid and accurate responses of the cell to changing environmental conditions.About:
This article is published in Journal of Molecular Biology.The article was published on 1999-10-22. It has received 2804 citations till now. The article focuses on the topics: Protein structure function & Intrinsically disordered proteins.read more
Citations
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Dynamic Behavior of an Intrinsically Unstructured Linker Domain Is Conserved in the Face of Negligible Amino Acid Sequence Conservation
TL;DR: The results of this analysis showed that many sites in the IULD are evolving neutrally, suggesting that dynamic behavior can be maintained in the absence of natural selection.
Journal ArticleDOI
Biophysical and computational fragment-based approaches to targeting protein^protein interactions: applications in structure-guided drug discovery
Anja Winter,Alicia P. Higueruelo,May Marsh,A.G. Sigurdardottir,William R. Pitt,Tom L. Blundell +5 more
TL;DR: The use of sensitive biophysical methods – nuclear magnetic resonance, X-ray crystallography, surface plasmon resonance, differential scanning fluorimetry or isothermal calorimetry – to screen and validate fragment binding may provide new leads for drug candidates that target protein–protein interactions and have therapeutic value.
Journal ArticleDOI
Folding of a Salivary Intrinsically Disordered Protein upon Binding to Tannins
Francis Canon,Renaud Ballivian,Renaud Ballivian,Fabien Chirot,Rodolphe Antoine,Pascale Sarni-Manchado,Jérôme Lemoine,Philippe Dugourd +7 more
TL;DR: The data demonstrate that IB5 undergoes an unfolded to folded structural transition upon binding with EgCG, demonstrating conformational adaptability of intrinsically disordered proteins bound to their targets in complex mixtures.
Journal ArticleDOI
Structure-based Inhibitor Design for the Intrinsically Disordered Protein c-Myc
TL;DR: The approach of IDP conformation sampling, binding site identification, and virtual screening for compounds that can bind to multiple conformations provides a useful strategy for structure-based drug discovery targeting IDPs.
Journal ArticleDOI
Towards the physical basis of how intrinsic disorder mediates protein function.
TL;DR: The experimental and computational approaches that may be integrated to address many important challenges of establishing a "structural" basis of IDP function are reviewed, and some of the key emerging ideas on how the conformational ensembles of IDPs may mediate function are discussed, especially in coupled binding and folding interactions.
References
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The Transcriptional Coactivators p300 and CBP Are Histone Acetyltransferases
TL;DR: It is demonstrated that p300/CBP acetylates nucleosomes in concert with PCAF, a novel class of acetyltransferases in that it does not have the conserved motif found among various other acetyl transferases.
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The Structural Basis of Estrogen Receptor/Coactivator Recognition and the Antagonism of This Interaction by Tamoxifen
Andrew K. Shiau,Danielle Barstad,Paula M. Loria,Lin Cheng,Peter J. Kushner,David A. Agard,Geoffrey L. Greene +6 more
TL;DR: Crystal structures of the human estrogen receptor alpha (hER alpha) ligand-binding domain (LBD) and the OHT-LBD complex reveal the two distinct mechanisms by which structural features of OHT promote this "autoinhibitory" helix 12 conformation.
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Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution
TL;DR: The X-ray crystal structure of a core synaptic fusion complex containing syntaxin-1A, synaptobrevin-II and SNAP-25B reveals a highly twisted and parallel four-helix bundle that differs from the bundles described for the haemagglutinin and HIV/SIV gp41 membrane-fusion proteins.
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Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.
Keh-Ming Pan,Michael J. Baldwin,J Nguyen,María Gasset,Ana Serban,Darlene Groth,Ingrid Mehlhorn,Ziwei Huang,Robert J. Fletterick,Fred E. Cohen +9 more
TL;DR: It is argued that the conversion of alpha-helices into beta-sheets underlies the formation of PrPSc, and it is likely that this conformational transition is a fundamental event in the propagation of prions.
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A signature motif in transcriptional co-activators mediates binding to nuclear receptors.
TL;DR: It is proposed that the LXXLL motif is a signature sequence that facilitates the interaction of different proteins with nuclear receptors, and is thus a defining feature of a new family of nuclear proteins.