Abstract：
:Protein folding and binding are analogous processes, in which the protein 'searches' for favourable intramolecular or intermolecular interactions on a funnelled energy landscape. Many eukaryotic proteins are disordered under physiological conditions, and fold into ordered structures only on binding to their cellular targets. The mechanism by which folding is coupled to binding is poorly understood, but it has been hypothesized on theoretical grounds that the binding kinetics may be enhanced by a 'fly-casting' effect, where the disordered protein binds weakly and non-specifically to its target and folds as it approaches the cognate binding site. Here we show, using NMR titrations and (15)N relaxation dispersion, that the phosphorylated kinase inducible activation domain (pKID) of the transcription factor CREB forms an ensemble of transient encounter complexes on binding to the KIX domain of the CREB binding protein. The encounter complexes are stabilized primarily by non-specific hydrophobic contacts, and evolve by way of an intermediate to the fully bound state without dissociation from KIX. The carboxy-terminal helix of pKID is only partially folded in the intermediate, and becomes stabilized by intermolecular interactions formed in the final bound state. Future applications of our method will provide new understanding of the molecular mechanisms by which intrinsically disordered proteins perform their diverse biological functions.
journal_name
Naturejournal_title
Natureauthors
Sugase K,Dyson HJ,Wright PEdoi
10.1038/nature05858subject
Has Abstractpub_date
2007-06-21 00:00:00pages
1021-5issue
7147eissn
0028-0836issn
1476-4687pii
nature05858journal_volume
447pub_type
杂志文章相关文献
NATURE文献大全abstract：:A long-standing problem in managing the behaviour of a collection of solid grains concerns the nature of the grain packing, a property that is typically controlled by how the grains are poured or shaken. Here we show that a systematic and controllable increase in granular packing can be induced by simply raising and t...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/442257a
更新日期：2006-07-20 00:00:00
abstract：:Vaccines against a variety of infectious diseases represent one of the great triumphs of medicine. The immune correlates of protection induced by most current vaccines seem to be mediated by long-lived humoral immune responses. By contrast, there are no currently available vaccines that are uniformly effective for dis...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35021239
更新日期：2000-08-17 00:00:00
abstract：:After an earthquake, numerous smaller shocks are triggered over distances comparable to the dimensions of the mainshock fault rupture, although they are rare at larger distances. Here we analyse the scaling of dynamic deformations (the stresses and strains associated with seismic waves) with distance from, and magnitu...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/437830a
更新日期：2005-10-06 00:00:00
abstract：:Quantum electrodynamics describes the interactions of electrons and photons. Electric charge (the gauge coupling constant) is energy dependent, and there is a previous claim that charge is affected by gravity (described by general relativity) with the implication that the charge is reduced at high energies. However, t...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature09506
更新日期：2010-11-04 00:00:00
abstract：:Modifications of histone proteins have essential roles in normal development and human disease. Recognition of modified histones by 'reader' proteins is a key mechanism that mediates the function of histone modifications, but how the dysregulation of these readers might contribute to disease remains poorly understood....
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-019-1842-7
更新日期：2020-01-01 00:00:00
abstract：:The RAD3 gene of Saccharomyces cerevisiae is required for excision repair of ultraviolet-damaged DNA and is essential for cell viability. The RAD3-encoded protein shares a high degree of homology with the human ERCC2(XPD) gene product. Mutations in XPD, besides causing the cancer-prone syndrome xeroderma pigmentosum, ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/367091a0
更新日期：1994-01-06 00:00:00
abstract：:The ras-related low-molecular-mass GTPases participate in signal transduction involving a variety of cellular functions, including cell-cycle progression, cellular differentiation, cytoskeletal organization, protein transport and secretion. The cycling of these proteins between GTP-bound and GDP-bound states is partia...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/359153a0
更新日期：1992-09-10 00:00:00
abstract：:Susceptibility of rodent cells to infection by ecotropic murine leukaemia viruses (MuLV) is determined by binding of the virus envelope to a membrane receptor that has multiple membrane-spanning domains. Cells infected by ecotropic MuLV synthesize envelope protein, gp70, which binds to this receptor, thereby preventin...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/352725a0
更新日期：1991-08-22 00:00:00
abstract：:The expression of immunodeficiency in patients with specific purine enzyme defects indicates a crucial role of the purine salvage pathway in the acquisition and expression of normal immune function. One current hypothesis links the failure of normal lymphocyte development in these diseases to the accumulation of deoxy...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/285494a0
更新日期：1980-06-12 00:00:00
abstract：:Human B cell stimulatory factor 2 (BSF-2) was originally characterized and isolated as a T cell-derived factor that caused the terminal maturation of activated B cells to immunoglobulin-producing cells. Molecular cloning of the complementary DNA predicts that BSF-2 is a protein of relative molecular mass (Mr) 26,000 s...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/332083a0
更新日期：1988-03-03 00:00:00
abstract：:Predation can be intense, creating strong direct and indirect effects throughout food webs. In addition, ecologists increasingly recognize that fluxes of organisms across ecosystem boundaries can have major consequences for community dynamics. Species with complex life histories often shift habitats during their life ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature03962
更新日期：2005-10-06 00:00:00
abstract：:In this Letter, the statement 'I.I. and A.B. performed computations at the NCI Australia' was missing from the Acknowledgements section. This has been corrected online. ...
journal_title：Nature
pub_type： 已发布勘误
doi：10.1038/s41586-019-1123-5
更新日期：2019-05-01 00:00:00
abstract：:In mammalian somatic-cell cycles, progression through the G1-phase restriction point and initiation of DNA replication are controlled by the ability of the retinoblastoma tumour-suppressor protein (pRb) family to regulate the E2F/DP transcription factors. Continuing transcription of E2F target genes beyond the G1/S tr...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/44611
更新日期：1999-10-21 00:00:00
abstract：:Men who develop metastatic castration-resistant prostate cancer (CRPC) invariably succumb to the disease. Progression to CRPC after androgen ablation therapy is predominantly driven by deregulated androgen receptor (AR) signalling. Despite the success of recently approved therapies targeting AR signalling, such as abi...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature13229
更新日期：2014-06-12 00:00:00
abstract：:Variations in atmospheric radiocarbon (14C) concentrations can be attributed either to changes in the carbon cycle--through the rate of radiocarbon removal from the atmosphere--or to variations in the production rate of 14C due to changes in solar activity or the Earth's magnetic field. The production rates of 10Be an...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35046041
更新日期：2000-11-30 00:00:00
abstract：:Antifreeze proteins provide fish with protection against the freezing effect of polar environments by binding to ice surfaces and inhibiting growth of ice crystals. We present the X-ray crystal structure at 1.5 A resolution of a lone alpha-helical antifreeze protein from winter flounder, which provides a detailed look...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/375427a0
更新日期：1995-06-01 00:00:00
abstract：:Caste differentiation and division of labour are the hallmarks of insect societies and at the root of their ecological success. Kin selection predicts that caste determination should result from environmentally induced differences in gene expression, a prediction largely supported by empirical data. However, two excep...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature01744
更新日期：2003-07-17 00:00:00
abstract：:Biodegradation of crude oil by bacterial activity--which has occurred in the majority of the Earth's oil reserves--is known to reduce greatly the quality of petroleum in reservoirs. For economically successful prospecting for oil, it is therefore important to understand the processes and conditions in geological forma...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35082535
更新日期：2001-06-28 00:00:00
abstract：:The evolution of animal personalities is a topic of primary importance in behavioural ecology. An intriguing empirical fact is the consistency of animal responses to repeated stresses or threats. Wolf et al. propose an evolutionary model to explain the emergence of consistent personalities. They show that a population...
journal_title：Nature
pub_type： 评论,杂志文章
doi：10.1038/nature06743
更新日期：2008-02-28 00:00:00
abstract：:Solitons are large-amplitude, spatially confined wave packets in nonlinear media. They occur in a wide range of physical systems, such as water surfaces, optical fibres, plasmas, Bose-Einstein condensates and magnetically ordered media. A distinguishing feature of soliton behaviour that is common to all systems, is th...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature02042
更新日期：2003-11-13 00:00:00
abstract：:Levels of gene expression underpin organismal phenotypes1,2, but the nature of selection that acts on gene expression and its role in adaptive evolution remain unknown1,2. Here we assayed gene expression in rice (Oryza sativa)3, and used phenotypic selection analysis to estimate the type and strength of selection on t...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-020-1997-2
更新日期：2020-02-01 00:00:00
abstract：:A chimaeric gene, consisting of the 5'-flanking region of a member of the Pisum sativum gene family encoding ribulose 1,5-bisphosphate carboxylase linked to the coding region of a bacterial chloramphenicol acetyltransferase gene, has been introduced into the genome of the plant Nicotiana tabacum using a Ti plasmid of ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/310115a0
更新日期：1984-07-12 00:00:00
abstract：:A large impact by a comet or meteorite releases an enormous amount of energy, which evaporates, melts and fractures the surrounding rocks. Distinctive features of such impacts are 'shatter cones', deformed rocks characterized by hierarchical striated features. Although such features have been used for decades as unequ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature00903
更新日期：2002-07-18 00:00:00
abstract：:What limits the rate at which sensory information can be transmitted across synaptic connections in the brain? High-frequency signalling is restricted to brief bursts at many central excitatory synapses, whereas graded ribbon-type synapses can sustain release and transmit information at high rates. Here we investigate...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature04509
更新日期：2006-02-23 00:00:00
abstract：:The nucleus of mammalian cells displays a distinct spatial segregation of active euchromatic and inactive heterochromatic regions of the genome1,2. In conventional nuclei, microscopy shows that euchromatin is localized in the nuclear interior and heterochromatin at the nuclear periphery1,2. Genome-wide chromosome conf...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-019-1275-3
更新日期：2019-06-01 00:00:00
abstract：:The ventral tegmental area (VTA) and nucleus accumbens (NAc) are essential for learning about environmental stimuli associated with motivationally relevant outcomes. The task of signalling such events, both rewarding and aversive, from the VTA to the NAc has largely been ascribed to dopamine neurons. The VTA also cont...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature11657
更新日期：2012-12-20 00:00:00
abstract：:The guanine nucleotide-binding stimulatory protein (Gs) couples hormone-receptor interaction to the activation of adenylate cyclase and the generation of cyclic AMP. Studies using frog neuroepithelium indicate that the sense of smell is mediated by a Gs-adenylate cyclase system, and this prompted us to test olfaction ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/322635a0
更新日期：1986-08-14 00:00:00
abstract：:Bananas (Musa spp.), including dessert and cooking types, are giant perennial monocotyledonous herbs of the order Zingiberales, a sister group to the well-studied Poales, which include cereals. Bananas are vital for food security in many tropical and subtropical countries and the most popular fruit in industrialized c...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature11241
更新日期：2012-08-09 00:00:00
abstract：:The gal operon of Escherichia coli is controlled by two independent promotors--one is activated and the other inhibited by cyclic AMP and cyclic AMP receptor protein. The two promotors are modulated, however, by the same operator locus and receptor protein. ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/279492a0
更新日期：1979-06-07 00:00:00
abstract：:Interest in attributing the risk of damaging weather-related events to anthropogenic climate change is increasing. Yet climate models used to study the attribution problem typically do not resolve the weather systems associated with damaging events such as the UK floods of October and November 2000. Occurring during t...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature09762
更新日期：2011-02-17 00:00:00
