Linking Folding and Binding

By Peter E. Wright, H. J. Dyson. Current Opinion in Structural Biology, 2009

1,014 citations recorded by the source corpus.

Many cellular proteins are intrinsically disordered and undergo folding, in whole or in part, upon binding to their physiological targets. The past few years have seen an exponential increase in papers describing characterization of intrinsically disordered proteins, both free and bound to targets. Although NMR spectroscopy remains the favored tool, a number of new biophysical techniques are proving exceptionally useful in defining the limits of the conformational ensembles. Advances have been made in prediction of the recognition elements in disordered proteins, in elucidating the kinetics and mechanism of the coupled folding and binding process, and in understanding the role of post-translational modifications in tuning the biological response. Here we review these and other recent advances that are providing new insights into the conformational propensities and interactions of intrinsically disordered proteins and are beginning to reveal general principles underlying their biological functions.

Subfields: Materials Chemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/50e355425453d93d00a39413a93eb891b6c29b65

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Citations in the corpus

Rosetta FlexPepDock ab-initio: Simultaneous Folding, Docking and Refinement of Peptides onto Their Receptors (2011, background): “These peptides often form a modular binding motif, which can be embedded in intrinsically unstructured protein regions and within flexible loops, in order to confer desired interactions [2,3,4,5].”
Evaluation of disorder predictions in CASP9 (2011, background): “…eukaryotes and prokaryotes8–10 and tend to be enriched for regulatory functions related to molecular recognition and signal transduc-The tion.11 –14 The number of experimentally verified IDPs and IDRs is rapidly rising15: the DisProt database16 currently contains annotations for more than 640…”
DisProt 7.0: a major update of the database of disordered proteins (2016, neutral): “…shown that in certain cases their function arises directly from the disordered state (entropic chains), whereas in many other cases their function em-anates from molecular recognition accompanied by induced folding to specific binding partners, such as another protein, RNA or DNA molecule (9,10).”
The roles of conditional disorder in redox proteins (2013, background): “On a positive note, studies of protein disorders have prompted the development and adaptation of modern technologies, especially in the field of nuclear magnetic resonance (NMR), small angle X-ray scattering (SAXS), and mass spectrometry [37,59–65,66 ,67,68].”
FuzDB: database of fuzzy complexes, a tool to develop stochastic structure-function relationships for protein complexes and higher-order assemblies (2016, background): “A common assumption is that while ID proteins/regions have excessive conformational freedom in their free state in solution, this becomes rather limited when they interact with their partners (4).”
A decade and a half of protein intrinsic disorder: Biology still waits for physics (2013, neutral): “1, 4, [11] [12] [13] [14] [15] 31, [70] [71] [72] [73] [76] [77] [78] [79] 131, 132, [134] [135] [136] [137] [138] [139] [140] [141] [142] [143] [144] [145] [146] [147] [148] [149] The conformational plasticity of IDPs/IDPRs provides them with a wide spectrum of exceptional functional advantages ove”
Mapping Residual Structure in Intrinsically Disordered Proteins at Residue Resolution Using Millisecond Hydrogen/Deuterium Exchange and Residue Averaging (2015, background): “Central to their functions in protein–protein interactions is the phenomenon of coupled folding and binding, where a disordered protein becomes folded upon engagement with its binding partner [6].”