GSTDTAP

浏览/检索结果: 共4条,第1-4条 帮助

限定条件                    
已选(0)清除 条数/页:   排序方式:
Structure of the human metapneumovirus polymerase phosphoprotein complex 期刊论文
NATURE, 2020, 577 (7789) : 275-+
作者:  Pan, Junhua;  Qian, Xinlei;  Lattmann, Simon;  El Sahili, Abbas;  Yeo, Tiong Han;  Jia, Huan;  Cressey, Tessa;  Ludeke, Barbara;  Noton, Sarah;  Kalocsay, Marian;  Fearns, Rachel;  Lescar, Julien
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/03

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause severe respiratory diseases in infants and elderly adults(1). No vaccine or effective antiviral therapy currently exists to control RSV or HMPV infections. During viral genome replication and transcription, the tetrameric phosphoprotein P serves as a crucial adaptor between the ribonucleoprotein template and the L protein, which has RNA-dependent RNA polymerase (RdRp), GDP polyribonucleotidyltransferase and cap-specific methyltransferase activities(2,3). How P interacts with L and mediates the association with the free form of N and with the ribonucleoprotein is not clear for HMPV or other major human pathogens, including the viruses that cause measles, Ebola and rabies. Here we report a cryo-electron microscopy reconstruction that shows the ring-shaped structure of the polymerase and capping domains of HMPV-L bound to a tetramer of P. The connector and methyltransferase domains of L are mobile with respect to the core. The putative priming loop that is important for the initiation of RNA synthesis is fully retracted, which leaves space in the active-site cavity for RNA elongation. P interacts extensively with the N-terminal region of L, burying more than 4,016 angstrom(2) of the molecular surface area in the interface. Two of the four helices that form the coiled-coil tetramerization domain of P, and long C-terminal extensions projecting from these two helices, wrap around the L protein in a manner similar to tentacles. The structural versatility of the four P protomers-which are largely disordered in their free state-demonstrates an example of a '  folding-upon-partner-binding'  mechanism for carrying out P adaptor functions. The structure shows that P has the potential to modulate multiple functions of L and these results should accelerate the design of specific antiviral drugs.


  
The stepwise assembly of the neonatal virome is modulated by breastfeeding 期刊论文
NATURE, 2020
作者:  Medina, Christopher B.;  Mehrotra, Parul;  Arandjelovic, Sanja;  Perrys, Justin S. A.;  Guo, Yizhan;  Morioka, Sho;  Barron, Brady;  Walk, Scott F.;  Ghesquiere, Bart;  Lorenz, Ulrike;  Krupnick, Alexander S.;  Ravichandran, Kodi S.
收藏  |  浏览/下载:36/0  |  提交时间:2020/07/03

The infant gut is colonized first by temperate bacteriophages induced from pioneer bacteria and later by viruses that replicate in human cells, the populations of which are modulated by breastfeeding.


The gut of healthy human neonates is usually devoid of viruses at birth, but quickly becomes colonized, which-in some cases-leads to gastrointestinal disorders(1-4). Here we show that the assembly of the viral community in neonates takes place in distinct steps. Fluorescent staining of virus-like particles purified from infant meconium or early stool samples shows few or no particles, but by one month of life particle numbers increase to 10(9) per gram, and these numbers seem to persist throughout life(5-7). We investigated the origin of these viral populations using shotgun metagenomic sequencing of virus-enriched preparations and whole microbial communities, followed by targeted microbiological analyses. Results indicate that, early after birth, pioneer bacteria colonize the infant gut and by one month prophages induced from these bacteria provide the predominant population of virus-like particles. By four months of life, identifiable viruses that replicate in human cells become more prominent. Multiple human viruses were more abundant in stool samples from babies who were exclusively fed on formula milk compared with those fed partially or fully on breast milk, paralleling reports that breast milk can be protective against viral infections(8-10). Bacteriophage populations also differed depending on whether or not the infant was breastfed. We show that the colonization of the infant gut is stepwise, first mainly by temperate bacteriophages induced from pioneer bacteria, and later by viruses that replicate in human cells  this second phase is modulated by breastfeeding.


  
Elemental signatures of Australopithecus africanus teeth reveal seasonal dietary stress 期刊论文
NATURE, 2019, 572 (7767) : 112-+
作者:  Joannes-Boyau, Renaud;  Adams, Justin W.;  Austin, Christine;  Arora, Manish;  Moffat, Ian;  Herries, Andy I. R.;  Tonge, Matthew P.;  Benazzi, Stefano;  Evans, Alistair R.;  Kullmer, Ottmar;  Wroe, Stephen;  Dosseto, Anthony;  Fiorenza, Luca
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/27
A Cryptosporidium PI(4)K inhibitor is a drug candidate for cryptosporidiosis 期刊论文
NATURE, 2017, 546 (7658) : 376-+
作者:  Manjunatha, Ujjini H.;  Vinayak, Sumiti;  Zambriski, Jennifer A.;  Chao, Alexander T.;  Sy, Tracy;  Noble, Christian G.;  Bonamy, Ghislain M. C.;  Kondreddi, Ravinder R.;  Zou, Bin;  Gedeck, Peter;  Brooks, Carrie F.;  Herbert, Gillian T.;  Sateriale, Adam;  Tandel, Jayesh;  Noh, Susan;  Lakshminarayana, Suresh B.;  Lim, Siau H.;  Goodman, Laura B.;  Bodenreider, Christophe;  Feng, Gu;  Zhang, Lijun;  Blasco, Francesca;  Wagner, Juergen;  Leong, F. Joel;  Striepen, Boris;  Diagana, Thierry T.
收藏  |  浏览/下载:6/0  |  提交时间:2019/04/09