Abstract：
:The battle for survival between bacteria and the viruses that infect them (phages) has led to the evolution of many bacterial defence systems and phage-encoded antagonists of these systems. Clustered regularly interspaced short palindromic repeats (CRISPR) and the CRISPR-associated (cas) genes comprise an adaptive immune system that is one of the most widespread means by which bacteria defend themselves against phages. We identified the first examples of proteins produced by phages that inhibit a CRISPR-Cas system. Here we performed biochemical and in vivo investigations of three of these anti-CRISPR proteins, and show that each inhibits CRISPR-Cas activity through a distinct mechanism. Two block the DNA-binding activity of the CRISPR-Cas complex, yet do this by interacting with different protein subunits, and using steric or non-steric modes of inhibition. The third anti-CRISPR protein operates by binding to the Cas3 helicase-nuclease and preventing its recruitment to the DNA-bound CRISPR-Cas complex. In vivo, this anti-CRISPR can convert the CRISPR-Cas system into a transcriptional repressor, providing the first example-to our knowledge-of modulation of CRISPR-Cas activity by a protein interactor. The diverse sequences and mechanisms of action of these anti-CRISPR proteins imply an independent evolution, and foreshadow the existence of other means by which proteins may alter CRISPR-Cas function.
journal_name
Naturejournal_title
Natureauthors
Bondy-Denomy J,Garcia B,Strum S,Du M,Rollins MF,Hidalgo-Reyes Y,Wiedenheft B,Maxwell KL,Davidson ARdoi
10.1038/nature15254subject
Has Abstractpub_date
2015-10-01 00:00:00pages
136-9issue
7571eissn
0028-0836issn
1476-4687pii
nature15254journal_volume
526pub_type
杂志文章相关文献
NATURE文献大全abstract：:Satellite observations have transformed our understanding of the Antarctic cryosphere. The continent holds the vast majority of Earth's fresh water, and blankets swathes of the Southern Hemisphere in ice. Reductions in the thickness and extent of floating ice shelves have disturbed inland ice, triggering retreat, acce...
journal_title：Nature
pub_type： 杂志文章,评审
doi：10.1038/s41586-018-0171-6
更新日期：2018-06-01 00:00:00
abstract：:Lake Victoria, together with its satellite lakes, harbours roughly 200 endemic forms of cichlid fishes that are classified as 'haplochromines' and yet the lake system is less than a million years old. This 'flock' has attracted attention because of the possibility that it evolved within the lake from one ancestral spe...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/347550a0
更新日期：1990-10-11 00:00:00
abstract：:The initiation of immunoglobulin-E (IgE)-mediated allergic responses requires the binding of IgE antibody to its high-affinity receptor, Fc epsilonRI. Crosslinking of Fc epsilonRI initiates an intracellular signal transduction cascade that triggers the release of mediators of the allergic response. The interaction of ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35018500
更新日期：2000-07-20 00:00:00
abstract：:The structure of an N-terminal fragment of CD4 has been determined to 2.4 A resolution. It has two tightly abutting domains connected by a continuous beta strand. Both have the immunoglobulin fold, but domain 2 has a truncated beta barrel and a non-standard disulphide bond. The binding sites for monoclonal antibodies,...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/348411a0
更新日期：1990-11-29 00:00:00
abstract：: ...
journal_title：Nature
pub_type： 新闻
doi：10.1038/d41586-018-07372-3
更新日期：2018-12-01 00:00:00
abstract：:Antigen recognition by T lymphocytes is mediated by cell-surface glycoproteins known as T-cell antigen receptors (TCRs). These are composed of alpha and beta, or gamma and delta, polypeptide chains with variable (V) and constant (C) regions. In contrast to alphabeta TCRs, which recognize antigen only as peptide fragme...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35172
更新日期：1998-01-29 00:00:00
abstract：:Io leaves a magnetic footprint on Jupiter's upper atmosphere that appears as a spot of ultraviolet emission that remains fixed underneath Io as Jupiter rotates. The specific physical mechanisms responsible for generating those emissions are not well understood, but in general the spot seems to arise because of an elec...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/415997a
更新日期：2002-02-28 00:00:00
abstract：:When an intense laser pulse is focused into a gas, the light-atom interaction that occurs as atoms are ionized results in an extremely nonlinear optical process--the generation of high harmonics of the driving laser frequency. Harmonics that extend up to orders of about 300 have been reported, some corresponding to ph...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35018029
更新日期：2000-07-13 00:00:00
abstract：:The injection of Rous sarcoma virus (RSV) into the wing web of newly hatched chicks causes a rapidly growing sarcomatous tumour which is palpable within 1 week of inoculation; and cultures of fibroblasts derived from chick embryos (CEF) and infected with RSV become rapidly transformed. Genetic studies have determined ...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/309552a0
更新日期：1984-06-07 00:00:00
abstract：:Resistance to infection and clearance of cell debris in mammals depend on the activation of the complement system, which is an important component of innate and adaptive immunity. Central to the complement system is the activated form of C3, called C3b, which attaches covalently to target surfaces to amplify complemen...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature05172
更新日期：2006-11-09 00:00:00
abstract：:Helium is used as a critical tracer throughout the Earth sciences, where its relatively simple isotopic systematics is used to trace degassing from the mantle, to date groundwater and to time the rise of continents. The hydrothermal system at Yellowstone National Park is famous for its high helium-3/helium-4 isotope r...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature12992
更新日期：2014-02-20 00:00:00
abstract：:Defects in insulin signalling are among the most common and earliest defects that predispose an individual to the development of type 2 diabetes. MicroRNAs have been identified as a new class of regulatory molecules that influence many biological functions, including metabolism. However, the direct regulation of insul...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature10112
更新日期：2011-06-08 00:00:00
abstract：:The clinical development of an inhibitor of cellular proteasome function suggests that compounds targeting other components of the ubiquitin-proteasome system might prove useful for the treatment of human malignancies. NEDD8-activating enzyme (NAE) is an essential component of the NEDD8 conjugation pathway that contro...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature07884
更新日期：2009-04-09 00:00:00
abstract：:The development of a multicellular organism involves a delicate balance among the processes of proliferation, differentiation and death. Naturally occurring cell death aids tissue remodelling, eliminates supernumerary cell populations and provides structural elements such as hair and skin. In the nervous system, selec...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/363166a0
更新日期：1993-05-13 00:00:00
abstract：:Reported widespread declines of wild and managed insect pollinators have serious consequences for global ecosystem services and agricultural production. Bees contribute approximately 80% of insect pollination, so it is important to understand and mitigate the causes of current declines in bee populations . Recent stud...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature11585
更新日期：2012-11-01 00:00:00
abstract：:The Environmental Protection Agency is preparing to regulate the biotechnology industry, claiming authority under the provisions of the Federal Toxic Substances Control Act (TOSCA) and the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA). In the agency's view, the products of recombinant DNA techniques can...
journal_title：Nature
pub_type： 新闻
doi：10.1038/306005a0
更新日期：1983-11-03 00:00:00
abstract：:Arising from C. J. Phiel, C. A. Wilson, V. M.-Y. Lee & P. S. Klein 423, 435-439 (2003)A major unresolved issue in Alzheimer's disease is identifying the mechanisms that regulate proteolytic processing of amyloid precursor protein (APP)-glycogen synthase kinase-3 (GSK-3) isozymes are thought to be important in this re...
journal_title：Nature
pub_type： 评论,杂志文章
doi：10.1038/nature10615
更新日期：2011-12-07 00:00:00
abstract：:The observations that atherosclerosis often occurs in non-smokers without elevated levels of low-density lipoprotein cholesterol, and that most atherosclerosis loci so far identified in mice do not affect systemic risk factors associated with atherosclerosis, suggest that as-yet-unidentified mechanisms must contribute...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature03527
更新日期：2005-05-26 00:00:00
abstract：:The complement system is a key part of the innate immune system, and is required for clearance of pathogens from the bloodstream. After exposure to pathogens, the third component of the complement system, C3, is cleaved to C3b which, after recruitment of factor B, initiates formation of the alternative pathway convert...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature05263
更新日期：2006-11-09 00:00:00
abstract：:Mitogen-activated protein kinases, MAP kinases or ERKs (extracellular signal-regulated kinases) are rapidly stimulated by growth-promoting factors acting on a variety of cell-surface receptors. In turn, ERKs phosphorylate and regulate key intracellular enzymes and transcription factors involved in the control of cellu...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/369418a0
更新日期：1994-06-02 00:00:00
abstract：:Understanding the determinants of healthy mental ageing is a priority for society today. So far, we know that intelligence differences show high stability from childhood to old age and there are estimates of the genetic contribution to intelligence at different ages. However, attempts to discover whether genetic cause...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature10781
更新日期：2012-01-18 00:00:00
abstract：:The extension of growing season at high northern latitudes seems increasingly clear from satellite observations of vegetation extent and duration. This extension is also thought to explain the observed increase in amplitude of seasonal variations in atmospheric CO2 concentration. Increased plant respiration and photos...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35015049
更新日期：2000-06-08 00:00:00
abstract：:A long-standing hypothesis posits that natural selection can favour two female strategies when density cycles. At low density, females producing many smaller progeny are favoured when the intrinsic rate of increase, r, governs population growth. At peak density, females producing fewer, high-quality, progeny are favou...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/35023149
更新日期：2000-08-31 00:00:00
abstract：:The murine cardioviruses, such as the Mengo and encephalomyocarditis viruses, and the bovine aphthoviruses, such as foot-and-mouth disease virus, are distinguished among positive-strand RNA viruses by the presence of long homopolymeric poly(C) tracts within their 5' noncoding sequences. Although the specific lengths (...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/343474a0
更新日期：1990-02-01 00:00:00
abstract：:Granular superconductivity occurs when microscopic superconducting grains are separated by non-superconducting regions; Josephson tunnelling between the grains establishes the macroscopic superconducting state. Although crystals of the copper oxide high-transition-temperature (high-Tc) superconductors are not granular...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/415412a
更新日期：2002-01-24 00:00:00
abstract：:The formation of a primordial crust is a critical step in the evolution of terrestrial planets but the timing of this process is poorly understood. The mineral zircon is a powerful tool for constraining crust formation because it can be accurately dated with the uranium-to-lead (U-Pb) isotopic decay system and is resi...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/s41586-018-0222-z
更新日期：2018-06-01 00:00:00
abstract：:Molecular processes that govern pathogenic features of erythrocyte invasion and cytoadherence in malaria are reliant on Plasmodium-specific Duffy-binding-like domains (DBLs). These cysteine-rich modules recognize diverse host cell-surface receptors during pathogenesis. DBLs of parasite erythrocyte-binding proteins med...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature04443
更新日期：2006-02-09 00:00:00
abstract：:Atlantic tropical cyclone activity, as measured by annual storm counts, reached anomalous levels over the past decade. The short nature of the historical record and potential issues with its reliability in earlier decades, however, has prompted an ongoing debate regarding the reality and significance of the recent ris...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature08219
更新日期：2009-08-13 00:00:00
abstract：:Calnexin, an endoplasmic reticulum transmembrane protein, represents a new type of molecular chaperone that selectively associates in a transient fashion with newly synthesized monomeric glycoproteins in HepG2 cells. Calnexin only recognizes glycoproteins when they are incompletely folded. Dissociation of glycoprotein...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/364771a0
更新日期：1993-08-26 00:00:00
abstract：:Where continental plates break apart, slip along multiple normal faults provides the required space for the Earth's crust to thin and subside. After initial rifting, however, the displacement on normal faults observed at the sea floor seems not to match the inferred extension. Here we show that crustal thinning can be...
journal_title：Nature
pub_type： 杂志文章
doi：10.1038/nature04608
更新日期：2006-03-16 00:00:00
