排序方式: 共有42条查询结果,搜索用时 140 毫秒
21.
Andersen CB Becker T Blau M Anand M Halic M Balar B Mielke T Boesen T Pedersen JS Spahn CM Kinzy TG Andersen GR Beckmann R 《Nature》2006,443(7112):663-668
Elongation factor eEF3 is an ATPase that, in addition to the two canonical factors eEF1A and eEF2, serves an essential function in the translation cycle of fungi. eEF3 is required for the binding of the aminoacyl-tRNA-eEF1A-GTP ternary complex to the ribosomal A-site and has been suggested to facilitate the clearance of deacyl-tRNA from the E-site. Here we present the crystal structure of Saccharomyces cerevisiae eEF3, showing that it consists of an amino-terminal HEAT repeat domain, followed by a four-helix bundle and two ABC-type ATPase domains, with a chromodomain inserted in ABC2. Moreover, we present the cryo-electron microscopy structure of the ATP-bound form of eEF3 in complex with the post-translocational-state 80S ribosome from yeast. eEF3 uses an entirely new factor binding site near the ribosomal E-site, with the chromodomain likely to stabilize the ribosomal L1 stalk in an open conformation, thus allowing tRNA release. 相似文献
22.
Anand N Murthy S Amann G Wernick M Porter LA Cukier IH Collins C Gray JW Diebold J Demetrick DJ Lee JM 《Nature genetics》2002,30(3):301-305
Telomeres in most immortal cells are maintained by the enzyme telomerase, allowing cells to divide indefinitely. Some telomerase-negative tumors and immortal cell lines maintain long heterogeneous telomeres by the ALT (alternative lengthening of telomeres) mechanism; such tumors are expected to be resistant to anti-telomerase drug therapies. Occasionally telomerase-negative Saccharomyces cerevisiae mutants survive, and 10% of them (type II survivors) have unstable telomeres. As in human ALT+ cells, short telomeres in yeast type II survivors lengthen abruptly; in yeast, this is dependent on the recombination proteins Rad52p and Rad50p. In human cells, ALT involves copying of sequence from a donor to a recipient telomere. We have characterized for the first time a class of complex telomere mutations seen only in ALT+ cells. The mutant telomeres are defined by the replacement of the progenitor telomere at a discrete point (fusion point) with a different telomere repeat array. Among 19 characterized fusion points, one occurred within the first six repeats of the telomere, indicating that these recombination-like events can occur anywhere within the telomere. One mutant telomere may have been involved in a secondary recombination-like mutation event, suggesting that these mutations are sporadic but ongoing in ALT+ cells. We also identified simple intra-allelic mutations at high frequency, which evidently contribute to telomere instability in ALT+ cells. 相似文献
23.
Griffith E Walker S Martin CA Vagnarelli P Stiff T Vernay B Al Sanna N Saggar A Hamel B Earnshaw WC Jeggo PA Jackson AP O'Driscoll M 《Nature genetics》2008,40(2):232-236
Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)--resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins--also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size. 相似文献
24.
会同林区林下植被与乔木层树种的关系 总被引:1,自引:0,他引:1
利用NMS排序和主成分分析方法,分离乔木层变量成林分结构和林冠物种组成2个主成分,并以其作为林下植被的环境因子,检查了上层乔木对林下植被多样性、物种组成和集群格局的影响.结果显示林冠的物种组成与林下植被的Shannon多样性显著相关,而林分结构跟多样性没有直接的联系;林分结构和林冠组成均显著地影响了林下植被的物种分布,... 相似文献
25.
NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens 总被引:1,自引:0,他引:1
PK Anand RK Malireddi JR Lukens P Vogel J Bertin M Lamkanfi TD Kanneganti 《Nature》2012,488(7411):389-393
Members of the intracellular nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family contribute to immune responses through activation of nuclear factor-κB (NF-κB), type I interferon and inflammasome signalling. Mice lacking the NLR family member NLRP6 were recently shown to be susceptible to colitis and colorectal tumorigenesis, but the role of NLRP6 in microbial infections and the nature of the inflammatory signalling pathways regulated by NLRP6 remain unclear. Here we show that Nlrp6-deficient mice are highly resistant to infection with the bacterial pathogens Listeria monocytogenes, Salmonella typhimurium and Escherichia coli. Infected Nlrp6-deficient mice had increased numbers of monocytes and neutrophils in circulation, and NLRP6 signalling in both haematopoietic and radioresistant cells contributed to increased susceptibility. Nlrp6 deficiency enhanced activation of mitogen-activated protein kinase (MAPK) and the canonical NF-κB pathway after Toll-like receptor ligation, but not cytosolic NOD1/2 ligation, in vitro. Consequently, infected Nlrp6-deficient cells produced increased levels of NF-κB- and MAPK-dependent cytokines and chemokines. Thus, our results reveal NLRP6 as a negative regulator of inflammatory signalling, and demonstrate a role for this NLR in impeding clearance of both Gram-positive and -negative bacterial pathogens. 相似文献
26.
A colloidal model system with an interaction tunable from hard sphere to soft and dipolar 总被引:4,自引:0,他引:4
Monodisperse colloidal suspensions of micrometre-sized spheres are playing an increasingly important role as model systems to study, in real space, a variety of phenomena in condensed matter physics--such as glass transitions and crystal nucleation. But to date, no quantitative real-space studies have been performed on crystal melting, or have investigated systems with long-range repulsive potentials. Here we demonstrate a charge- and sterically stabilized colloidal suspension--poly(methyl methacrylate) spheres in a mixture of cycloheptyl (or cyclohexyl) bromide and decalin--where both the repulsive range and the anisotropy of the interparticle interaction potential can be controlled. This combination of two independent tuning parameters gives rise to a rich phase behaviour, with several unusual colloidal (liquid) crystalline phases, which we explore in real space by confocal microscopy. The softness of the interaction is tuned in this colloidal suspension by varying the solvent salt concentration; the anisotropic (dipolar) contribution to the interaction potential can be independently controlled with an external electric field ranging from a small perturbation to the point where it completely determines the phase behaviour. We also demonstrate that the electric field can be used as a pseudo-thermodynamic temperature switch to enable real-space studies of melting transitions. We expect studies of this colloidal model system to contribute to our understanding of, for example, electro- and magneto-rheological fluids. 相似文献
27.
S. P. Kaur P. S. Chaudhry S. R. Anand 《Cellular and molecular life sciences : CMLS》1976,32(4):436-438
Summary Buffalo sperm acrosome resembles its counterpart in other species, being rich in hydrolytic enzymes. Of the enzyme activities estimated, acid phosphatase, -N-acetylglucosaminidase and hyaluronidase were low compared to those of ram semen. However, the aryl sulphatase activity was high. GOT activity estimated in sperm preparation may not be of acrosomal origin.NDRI publication No. 75-129.We should like to thank Dr.D. Sundaresan, the Director for encouragement and the Indian Council of Agricultural Research, New Delhi for partially funding this work. One of the authors (PSC) was recipient of a UGC junior fellowship. 相似文献
28.
Rivière JB Mirzaa GM O'Roak BJ Beddaoui M Alcantara D Conway RL St-Onge J Schwartzentruber JA Gripp KW Nikkel SM Worthylake T Sullivan CT Ward TR Butler HE Kramer NA Albrecht B Armour CM Armstrong L Caluseriu O Cytrynbaum C Drolet BA Innes AM Lauzon JL Lin AE Mancini GM Meschino WS Reggin JD Saggar AK Lerman-Sagie T Uyanik G Weksberg R Zirn B Beaulieu CL;Finding of Rare Disease Genes 《Nature genetics》2012,44(8):934-940
Megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features. We performed exome sequencing in 3 families with MCAP or MPPH, and our initial observations were confirmed in exomes from 7 individuals with MCAP and 174 control individuals, as well as in 40 additional subjects with megalencephaly, using a combination of Sanger sequencing, restriction enzyme assays and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in 23 individuals with MCAP and 1 with MPPH. Our data highlight the central role of PI3K-AKT signaling in vascular, limb and brain development and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism. 相似文献
29.
Vithana EN Morgan P Sundaresan P Ebenezer ND Tan DT Mohamed MD Anand S Khine KO Venkataraman D Yong VH Salto-Tellez M Venkatraman A Guo K Hemadevi B Srinivasan M Prajna V Khine M Casey JR Inglehearn CF Aung T 《Nature genetics》2006,38(7):755-757
Congenital hereditary endothelial dystrophy (CHED) is a heritable, bilateral corneal dystrophy characterized by corneal opacification and nystagmus. We describe seven different mutations in the SLC4A11 gene in ten families with autosomal recessive CHED. Mutations in SLC4A11, which encodes a membrane-bound sodium-borate cotransporter, cause loss of function of the protein either by blocking its membrane targeting or nonsense-mediated decay. 相似文献
30.
Schunkert H König IR Kathiresan S Reilly MP Assimes TL Holm H Preuss M Stewart AF Barbalic M Gieger C Absher D Aherrahrou Z Allayee H Altshuler D Anand SS Andersen K Anderson JL Ardissino D Ball SG Balmforth AJ Barnes TA Becker DM Becker LC Berger K Bis JC Boekholdt SM Boerwinkle E Braund PS Brown MJ Burnett MS Buysschaert I;Cardiogenics Carlquist JF Chen L Cichon S Codd V Davies RW Dedoussis G Dehghan A Demissie S Devaney JM Diemert P Do R Doering A Eifert S Mokhtari NE Ellis SG Elosua R 《Nature genetics》2011,43(4):333-338
We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10?? and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits. 相似文献