Abstract:
:Cyclosporin A, a cyclic undecapeptide, is a potent immunosuppressant that binds to a peptidyl-prolyl cis-trans isomerase of 165 amino acids, cyclophilin. The cyclosporin A/cyclophilin complex inhibits the calcium- and calmodulin-dependent phosphatase, calcineurin, resulting in a failure to activate genes encoding interleukin-2 and other lymphokines. The three-dimensional structures of uncomplexed cyclophilin, a tetrapeptide/cyclophilin complex, and cyclosporin A when bound to cyclophilin have been reported. However, the structure of the cyclosporin A/cyclophilin complex has not been determined. Here we present the solution structure of the cyclosporin A/cyclophilin complex obtained by heteronuclear three-dimensional NMR spectroscopy. The structure, one of the largest determined by NMR, differs from proposed models of the complex and is analysed in terms of the binding interactions and structure/activity relationships for CsA analogues.
journal_name
Naturejournal_title
Natureauthors
Thériault Y,Logan TM,Meadows R,Yu L,Olejniczak ET,Holzman TF,Simmer RL,Fesik SWdoi
10.1038/361088a0subject
Has Abstractpub_date
1993-01-07 00:00:00pages
88-91issue
6407eissn
0028-0836issn
1476-4687journal_volume
361pub_type
杂志文章相关文献
NATURE文献大全abstract::The theory of electric polarization in crystals defines the dipole moment of an insulator in terms of a Berry phase (geometric phase) associated with its electronic ground state. This concept not only solves the long-standing puzzle of how to calculate dipole moments in crystals, but also explains topological band str...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature25777
更新日期:2018-03-14 00:00:00
abstract::The midbrain region periaqueductal grey (PAG) is rich in opioid receptors and endogenous opioids and is a major target of analgesic action in the central nervous system. It has been proposed that the analgesic effect of opioids on the PAG works by suppressing the inhibitory influence of the neurotransmitter GABA (gamm...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/37610
更新日期:1997-12-11 00:00:00
abstract::Enhancers increase the frequency of transcription initiation from linked promoter elements, most probably as a result of the binding of specific proteins to the enhancer. The polyomavirus early region is expressed in differentiated mouse cells but not in undifferentiated embryonal carcinoma (EC) cells. This host range...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/328087a0
更新日期:1987-07-02 00:00:00
abstract::Protein modification by the conjugation of ubiquitin moieties--ubiquitination--plays a major part in many biological processes, including cell cycle and apoptosis. The enzymes that mediate ubiquitin-conjugation have been well-studied, but much less is known about the ubiquitin-specific proteases that mediate de-ubiqui...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01811
更新日期:2003-08-14 00:00:00
abstract::Large-scale chromosome structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on chromosome conformation capture (3C) assess contacts for millions of loci simultaneously, but do so by averaging chromosome conformations from mill...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12593
更新日期:2013-10-03 00:00:00
abstract::The regulation of intracellular pH (pHi) is essential for normal cell function, and controlled changes in pHi may play a central role in cell activation. Sodium-dependent Cl-HCO3 exchange is the dominant mechanism of pHi regulation in the invertebrate cells examined, and also occurs in mammalian cells. The transporter...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/332262a0
更新日期:1988-03-17 00:00:00
abstract::Acetylcholine (ACh) released on vagal stimulation reduces the heart rate by increasing K+ conductance of pacemaker cells in the sinoatrial (S-A) node. Fluctuation analysis of ACh-activated currents in pacemaker tissue showed this to be due to opening of a separate class of K+ channels gated by muscarinic ACh receptors...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/303250a0
更新日期:1983-05-19 00:00:00
abstract::The 2.2 A crystal structure of activated rod transducin, Gt alpha.GTP gamma S, shows the bound GTP gamma S molecule occluded deep in a cleft between a domain structurally homologous to small GTPases and a helical domain unique to heterotrimeric G proteins. The structure, when combined with biochemical and genetic stud...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/366654a0
更新日期:1993-12-16 00:00:00
abstract::The crab Xenograpsus testudinatus lives at enormously high densities around the sulphur-rich hydrothermal vents found in shallow waters off Taiwan, even though this acidic environment is low in nutrients. Here we show that these crabs swarm out of their crevices at slack water and feed on the vast numbers of zooplankt...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/432969a
更新日期:2004-12-23 00:00:00
abstract::The structure-function relationship of the nicotinic acetylcholine receptor (AChR) has been effectively studied by the combination of complementary DNA manipulation and single-channel current analysis. Previous work with chimaeras between the Torpedo californica and bovine AChR delta-subunits has shown that the region...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/335645a0
更新日期:1988-10-13 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature
pub_type: 已发布勘误
doi:10.1038/s41586-020-2517-0
更新日期:2020-08-01 00:00:00
abstract::Magnetic fields play a part in almost all stages of stellar evolution. Most low-mass stars, including the Sun, show surface fields that are generated by dynamo processes in their convective envelopes. Intermediate-mass stars do not have deep convective envelopes, although 10 per cent exhibit strong surface fields that...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature16171
更新日期:2016-01-21 00:00:00
abstract::The vertical structure of the recent Arctic warming contains information about the processes governing Arctic climate trends. Graversen et al. argue, on the basis of ERA-40 reanalysis data, that a distinct maximum in 1979-2001 warm-season (April-October) Arctic temperature trends appears around 3 km above ground. Here...
journal_title:Nature
pub_type: 评论,杂志文章
doi:10.1038/nature07257
更新日期:2008-09-11 00:00:00
abstract::Activation of a visual pigment molecule to initiate phototransduction requires a minimum energy, Ea, that need not be wholly derived from a photon, but may be supplemented by heat. Theory predicts that absorbance at very long wavelengths declines with the fraction of molecules that have a sufficient complement of ther...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35003242
更新日期:2000-01-13 00:00:00
abstract::Activity-induced changes in the efficacy of synaptic transmission between neurones are central to several prominent theories of learning. In both in vivo and in vitro preparations of the hippocampus, a conditioning high-frequency stimulus delivered to afferent fibres results in a long-term potentiation of synaptic tra...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/320529a0
更新日期:1986-04-10 00:00:00
abstract::The reaction mechanism of protein folding by the chaperonin GroEL and its regulator GroES has been defined. GroES and substrate protein counteract each other's effects on GroEL: whereas GroES stabilizes GroEL in the ADP-bound state, binding of unfolded polypeptide within the cavity of the GroEL cylinder triggers ADP a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/366228a0
更新日期:1993-11-18 00:00:00
abstract::Direct lineage reprogramming represents a remarkable conversion of cellular and transcriptome states. However, the intermediate stages through which individual cells progress during reprogramming are largely undefined. Here we use single-cell RNA sequencing at multiple time points to dissect direct reprogramming from ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature18323
更新日期:2016-06-16 00:00:00
abstract::Neurons in the brain behave as nonlinear oscillators, which develop rhythmic activity and interact to process information. Taking inspiration from this behaviour to realize high-density, low-power neuromorphic computing will require very large numbers of nanoscale nonlinear oscillators. A simple estimation indicates t...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature23011
更新日期:2017-07-26 00:00:00
abstract::Adenosine is a potent modulator of transmitter release at a variety of synapses. The adenosine A1 receptor is assumed to reside in presynaptic terminals and to function as a negative autoreceptor. How adenosine reduces transmitter release is uncertain; it may reduce the calcium influx during nerve terminal depolarizat...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/365256a0
更新日期:1993-09-16 00:00:00
abstract::The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence. The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours, but our understanding of the interaction between these two brain regions has been limited by the inability to man...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10194
更新日期:2011-06-29 00:00:00
abstract::Using visual information to guide behaviour requires storage in a temporary buffer, known as visual short-term memory (VSTM), that sustains attended information across saccades and other visual interruptions. There is growing debate on whether VSTM capacity is limited to a fixed number of objects or whether it is vari...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04262
更新日期:2006-03-02 00:00:00
abstract::For more than 140 years, pollen tube guidance in flowering plants has been thought to be mediated by chemoattractants derived from target ovules. However, there has been no convincing evidence of any particular molecule being the true attractant that actually controls the navigation of pollen tubes towards ovules. Eme...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07882
更新日期:2009-03-19 00:00:00
abstract::The hippocampus is an important part of the limbic system in the human brain that has essential roles in spatial navigation and the consolidation of information from short-term memory to long-term memory1,2. Here we use single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing (ATAC-se...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1917-5
更新日期:2020-01-01 00:00:00
abstract::Aquaporin (AQP) water-channel proteins are freely permeated by water but not by ions or charged solutes. Although mammalian aquaporins were believed to be located in plasma membranes, rat AQP6 is restricted to intracellular vesicles in renal epithelia. Here we show that AQP6 is functionally distinct from other known a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/46045
更新日期:1999-11-11 00:00:00
abstract::The brain has generally been considered an insulin-independent organ, because insulin does not apparently exert a direct effect on brain glucose consumption. Recently, however, insulin receptors have been detected throughout the central nervous system (CNS) of several species. Since important insights into the functio...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/282623a0
更新日期:1979-12-06 00:00:00
abstract::The methylation of vertebrate DNA at the 5-position of approximately 3-10% of its cytosine residues occurs in a sequence-specific and tissue-specific manner and has been implicated in the control of transcription. How these differences are established and how they mediate the initiation or maintenance of transcription...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/308293a0
更新日期:1984-03-15 00:00:00
abstract::Constructing agents with planning capabilities has long been one of the main challenges in the pursuit of artificial intelligence. Tree-based planning methods have enjoyed huge success in challenging domains, such as chess1 and Go2, where a perfect simulator is available. However, in real-world problems, the dynamics ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-03051-4
更新日期:2020-12-01 00:00:00
abstract::Photosynthetic dinoflagellates are important aquatic primary producers and notorious causes of toxic 'red tides'. Typical dinoflagellate chloroplasts differ from all other plastids in having a combination of three envelope membranes and peridinin-chlorophyll a/c light-harvesting pigments. Despite evidence of a dinofla...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/22099
更新日期:1999-07-08 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 评论,新闻
doi:10.1038/d41586-019-00393-6
更新日期:2019-02-01 00:00:00
abstract::Disruption of the normal regulation of cell-cycle progression and division lies at the heart of the events leading to cancer. Complex networks of regulatory factors, the tumour microenvironment and stress signals, such as those resulting from damaged DNA, dictate whether cancer cells proliferate or die. Recent progres...
journal_title:Nature
pub_type: 杂志文章,评审
doi:10.1038/nature03095
更新日期:2004-11-18 00:00:00