Abstract:
:DNA replication in eukaryotes is strictly regulated by several mechanisms. A central step in this replication is the assembly of the heterohexameric minichromosome maintenance (MCM2-7) helicase complex at replication origins during G1 phase as an inactive double hexamer. Here, using cryo-electron microscopy, we report a near-atomic structure of the MCM2-7 double hexamer purified from yeast G1 chromatin. Our structure shows that two single hexamers, arranged in a tilted and twisted fashion through interdigitated amino-terminal domain interactions, form a kinked central channel. Four constricted rings consisting of conserved interior β-hairpins from the two single hexamers create a narrow passageway that tightly fits duplex DNA. This narrow passageway, reinforced by the offset of the two single hexamers at the double hexamer interface, is flanked by two pairs of gate-forming subunits, MCM2 and MCM5. These unusual features of the twisted and tilted single hexamers suggest a concerted mechanism for the melting of origin DNA that requires structural deformation of the intervening DNA.
journal_name
Naturejournal_title
Natureauthors
Li N,Zhai Y,Zhang Y,Li W,Yang M,Lei J,Tye BK,Gao Ndoi
10.1038/nature14685subject
Has Abstractpub_date
2015-08-13 00:00:00pages
186-91issue
7564eissn
0028-0836issn
1476-4687pii
nature14685journal_volume
524pub_type
杂志文章相关文献
NATURE文献大全abstract::Climate strongly affects the production of sediment from mountain catchments as well as its transport and deposition within adjacent sedimentary basins. However, identifying climatic influences on basin stratigraphy is complicated by nonlinearities, feedback loops, lag times, buffering and convergence among processes ...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/nature11513
更新日期:2012-11-01 00:00:00
abstract::The quantum-level interplay between geometry, topology and correlation is at the forefront of fundamental physics1-15. Kagome magnets are predicted to support intrinsic Chern quantum phases owing to their unusual lattice geometry and breaking of time-reversal symmetry14,15. However, quantum materials hosting ideal spi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2482-7
更新日期:2020-07-01 00:00:00
abstract::In the coming decades, a crucial challenge for humanity will be meeting future food demands without undermining further the integrity of the Earth's environmental systems. Agricultural systems are already major forces of global environmental degradation, but population growth and increasing consumption of calorie- and...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11420
更新日期:2012-10-11 00:00:00
abstract::The masses of the supermassive black holes found in galaxy bulges are correlated with a multitude of galaxy properties, leading to suggestions that galaxies and black holes may evolve together. The number of reliably measured black-hole masses is small, and the number of methods for measuring them is limited, holding ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11819
更新日期:2013-02-21 00:00:00
abstract::An ongoing challenge in chemical research is to design catalysts that select the outcomes of the reactions of complex molecules. Chemists rely on organocatalysts or transition metal catalysts to control stereoselectivity, regioselectivity and periselectivity (selectivity among possible pericyclic reactions). Nature ac...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2743-5
更新日期:2020-10-01 00:00:00
abstract::A search for general regulators of cancer metastasis has yielded a set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential. Here we show that restoring the expression of these microRNAs in malignant cells suppresses lung and bone metastasis by human cancer c...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06487
更新日期:2008-01-10 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a degenerative disorder of motor neurons in the cortex, brainstem and spinal cord. Its cause is unknown and it is uniformly fatal, typically within five years. About 10% of cases are inherited as an autosomal dominant trait, with high penetrance after the sixth decade. In most in...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/362059a0
更新日期:1993-03-04 00:00:00
abstract::A hybrid gene was constructed between the beta-lactamase gene of plasmid pBR322 and the cloned coding sequence for rat growth hormone. This gene is expressed in bacteria and growth hormone sequences are detectable by immunological methods. ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/276795a0
更新日期:1978-12-21 00:00:00
abstract::Interstellar dust is responsible, through surface reactions, for the creation of molecular hydrogen, the main component of the interstellar clouds in which new stars form. Intermediate between small, gas-phase molecules and dust are the polycyclic aromatic hydrocarbons (PAHs). Such molecules could account for 2-30% of...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/380227a0
更新日期:1996-03-21 00:00:00
abstract::CDKN2A (INK4a/ARF) is frequently disrupted in various types of human cancer, and germline mutations of this locus can confer susceptibility to melanoma and other tumours. However, because CDKN2A encodes two distinct cell cycle inhibitory proteins, p16INK4a and p14ARF (p19Arf in mice), the mechanism of tumour suppressi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35092584
更新日期:2001-09-06 00:00:00
abstract::Several hormones and neurotransmitters raise the cytosolic free Ca2+ concentration by stimulating the influx of Ca2+ and/or by mobilizing stored Ca2+. However, the link between the agonist receptor on the cell surface and the organelle(s) from which Ca2+ is mobilized is unknown. One feature of the agonists that increa...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/309562a0
更新日期:1984-06-07 00:00:00
abstract::Splicing of the Tetrahymena ribosomal intron was first studied by Cech et al., who subsequently demonstrated that the intron RNA catalyses its own excision from a primary transcript to yield mature ribosomal RNA. This intron shares several short conserved sequences and a common secondary structure with several other i...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/322083a0
更新日期:1986-07-03 00:00:00
abstract::In several well-characterized site-specific recombination systems it has been shown that, for efficient recombination, the two recombining sites must have identical DNA sequences across the region between the staggered points of exchange. The precise DNA sequence of this overlap region, however, appears to be of littl...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/332861a0
更新日期:1988-04-28 00:00:00
abstract::Despite decades of research, the identity of the cells generating the first haematopoietic cells in mammalian embryos is unknown. Indeed, whether blood cells arise from mesodermal cells, mesenchymal progenitors, bipotent endothelial-haematopoietic precursors or haemogenic endothelial cells remains controversial. Proxi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07760
更新日期:2009-02-12 00:00:00
abstract::Homeostasis is a biological principle for regulation of essential physiological parameters within a set range. Behavioural responses due to deviation from homeostasis are critical for survival, but motivational processes engaged by physiological need states are incompletely understood. We examined motivational charact...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14416
更新日期:2015-05-14 00:00:00
abstract::Translation initiation determines both the quantity and identity of the protein that is encoded in an mRNA by establishing the reading frame for protein synthesis. In eukaryotic cells, numerous translation initiation factors prepare ribosomes for polypeptide synthesis; however, the underlying dynamics of this process ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-019-1561-0
更新日期:2019-09-01 00:00:00
abstract::In many cell types, receptor-mediated Ca2+ release from internal stores is followed by Ca2+ influx across the plasma membrane. The sustained entry of Ca2+ is thought to result partly from the depletion of intracellular Ca2+ pools. Most investigations have characterized Ca2+ influx indirectly by measuring Ca(2+)-activa...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/355353a0
更新日期:1992-01-23 00:00:00
abstract::Fireflies communicate with each other by emitting yellow-green to yellow-orange brilliant light. The bioluminescence reaction, which uses luciferin, Mg-ATP and molecular oxygen to yield an electronically excited oxyluciferin species, is carried out by the enzyme luciferase. Visible light is emitted during relaxation o...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04542
更新日期:2006-03-16 00:00:00
abstract::Non-small-cell lung cancer is the leading cause of cancer-related death worldwide. Chemotherapies such as the topoisomerase II (TopoII) inhibitor etoposide effectively reduce disease in a minority of patients with this cancer; therefore, alternative drug targets, including epigenetic enzymes, are under consideration f...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14122
更新日期:2015-04-09 00:00:00
abstract::The heterotrimeric G proteins mediate a variety of cellular processes by coupling transmembrane receptors to different effector molecules, including adenylyl cyclases and inositol-phospholipid-specific phospholipase C (PLC)1-3. Activation of adenylyl cyclases results in the production of cyclic AMP and activation of c...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/382083a0
更新日期:1996-07-04 00:00:00
abstract::Ice flow along land-terminating margins of the Greenland Ice Sheet (GIS) varies considerably in response to fluctuating inputs of surface meltwater to the bed of the ice sheet. Such inputs lubricate the ice-bed interface, transiently speeding up the flow of ice. Greater melting results in faster ice motion during summ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature15722
更新日期:2015-10-29 00:00:00
abstract::A variety of observations indicate that mid-ocean ridges produce less crust at spreading rates below 20 mm yr(-1) (refs 1-3), reflecting changes in fundamental ridge processes with decreasing spreading rate. The nature of these changes, however, remains uncertain, with end-member explanations being decreasing shallow ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03140
更新日期:2004-12-09 00:00:00
abstract::A cholecystokinin (CCK)-inactivating peptidase was purified and identified as a membrane-bound isoform of tripeptidyl peptidase II (EC 3.4.14.10), a cytosolic subtilisin-like peptidase of previously unknown functions. The peptidase was found in neurons responding to cholecystokinin, as well as in non-neuronal cells. B...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/380403a0
更新日期:1996-04-04 00:00:00
abstract::Adipocyte fatty-acid-binding protein, aP2 (FABP4) is expressed in adipocytes and macrophages, and integrates inflammatory and metabolic responses. Studies in aP2-deficient mice have shown that this lipid chaperone has a significant role in several aspects of metabolic syndrome, including type 2 diabetes and atheroscle...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature05844
更新日期:2007-06-21 00:00:00
abstract::Alzheimer's disease (AD) affects more than 30% of people over 80 years of age. The aetiology and pathogenesis of this progressive dementia is poorly understood, but symptomatic disease is associated histopathologically with amyloid plaques, neurofibrillary tangles and neuronal loss primarily in the temporal lobe and n...
journal_title:Nature
pub_type: 杂志文章,收录出版
doi:10.1038/354476a0
更新日期:1991-12-12 00:00:00
abstract::Ribosomes are translational machineries that catalyse protein synthesis. Ribosome structures from various species are known at the atomic level, but obtaining the structure of the human ribosome has remained a challenge; efforts to address this would be highly relevant with regard to human diseases. Here we report the...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14427
更新日期:2015-04-30 00:00:00
abstract::Many chemical and physical systems can occur in two forms distinguished solely by being mirror images of each other. This phenomenon, known as chirality, is important in biochemistry, where reactions involving chiral molecules often require the participation of one specific enantiomer (mirror image) of the two possibl...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35016043
更新日期:2000-06-22 00:00:00
abstract::Naturally occurring peptides with biological actions have in most cases been detected by observing their biological activities in crude extracts and their isolation has been followed using bioassays. As a complement to the classical biological detection systems, we have proposed a chemical detection system based on fr...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/285417a0
更新日期:1980-06-05 00:00:00
abstract::Zygotic genome activation in metazoans typically occurs several hours to a day after fertilization, and thus maternal RNAs and proteins drive early animal embryo development. In plants, despite several molecular studies of post-fertilization transcriptional activation, the timing of zygotic genome activation remains a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature13620
更新日期:2014-10-30 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 新闻
doi:10.1038/d41586-018-07463-1
更新日期:2018-11-01 00:00:00