Awards season is upon us... - p1117

doi:10.1038/nsmb1109-1117

The 2009 Nobel Prize for Physiology or Medicine goes to telomerase researchers, the Lasker Award to nuclear reprogramming pioneers, and crystallographers are awarded the Chemistry Nobel once again.

Full Text - Awards season is upon us... | PDF (194 KB) - Awards season is upon us...

How do transcription factors select specific binding sites in the genome? - pp1118 - 1120

Yongping Pan, Chung-Jung Tsai, Buyong Ma & Ruth Nussinov

doi:10.1038/nsmb1109-1118

How does a transcription factor select a specific DNA response element given the presence of degenerate sequences? To date, this question has largely been viewed from the standpoint of DNA sequence variability and transcription factor binding affinity under steady-state conditions. Here we propose that to address this problem, it is also necessary to account for fluctuating cellular conditions. These lead to dynamic changes in the ensemble of protein (and DNA) conformational states via allosteric effects.

Full Text - How do transcription factors select specific binding sites in the genome? | PDF (474 KB) - How do transcription factors select specific binding sites in the genome?

Glycan terminator - pp1121 - 1122

James C Paulson & Christoph Rademacher

doi:10.1038/nsmb1109-1121

Influenza virus binding to host cells and neutrophil trafficking to sites of inflammation are diverse aspects of biology mediated by receptor recognition of sialic acids that terminate glycans on cell surface glycoproteins and glycolipids. The first crystal structure of a mammalian sialyltransferase provides insights into the biosynthesis of the rich spectrum of sialic acid–containing glycans in the mammalian glycome.

Full Text - Glycan terminator | PDF (318 KB) - Glycan terminator

See also: Brief Communication by Rao et al.

Tracking rates of transcription and splicing in vivo - pp1123 - 1124

M Behfar Ardehali & John T Lis

doi:10.1038/nsmb1109-1123

A relatively simple but powerful method to measure RNA polymerase II transcription elongation as well as co-transcriptional RNA splicing rates at many genes in vivo is described in this issue. The results demonstrate a rather uniform, and high, elongation rate at large human genes and co-transcriptional pre-mRNA splicing of both U2- and U12-dependent primary transcripts.

Full Text - Tracking rates of transcription and splicing in vivo | PDF (271 KB) - Tracking rates of transcription and splicing in vivo

See also: Article by Singh & Padgett

A more structured metabolome - pp1125 - 1126

Matthew J Betts & Robert B Russell

doi:10.1038/nsmb1109-1125

A recent study has put together the three-dimensional structures of proteins involved in the central metabolism of one organism, providing insight into the evolution of metabolic networks.

Full Text - A more structured metabolome | PDF (391 KB) - A more structured metabolome

Research highlights - p1127

doi:10.1038/nsmb1109-1127

Full Text - Research highlights | PDF (128 KB) - Research highlights

Rates of in situ transcription and splicing in large human genes - pp1128 - 1133

Jarnail Singh & Richard A Padgett

doi:10.1038/nsmb.1666

Rates of in vivo transcription have proven hard to pin down, especially across long mammalian genes that can contain lengthy introns. Using DRB inhibition followed by release, the rates of transcription of multiple human genes are now measured and splicing rates of both U2- and U12-dependent introns are assessed.

Abstract - Rates of : in situ: transcription and splicing in large human genes | Full Text - Rates of in situ transcription and splicing in large human genes | PDF (781 KB) - Rates of in situ transcription and splicing in large human genes | Supplementary information

See also: News and Views by Ardehali & Lis

A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein - pp1134 - 1140

Wataru Kamitani, Cheng Huang, Krishna Narayanan, Kumari G Lokugamage & Shinji Makino

doi:10.1038/nsmb.1680

The SARS coronavirus protein nsp1 can suppress host gene expression at a post-transcriptional level, with previous work showing a reduction in mRNA abundance. Now a direct effect on protein synthesis is revealed, as nsp1 modifies transcripts and also inactivates the 40S ribosomal subunit.

Abstract - A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein | Full Text - A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein | PDF (1,450 KB) - A two-pronged strategy to suppress host protein synthesis by SARS coronavirus Nsp1 protein | Supplementary information

Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain - pp1141 - 1147

Shinji Tsutsumi, Mehdi Mollapour, Christian Graf, Chung-Tien Lee, Bradley T Scroggins, Wanping Xu, Lenka Haslerova, Martin Hessling, Anna A Konstantinova, Jane B Trepel, Barry Panaretou, Johannes Buchner, Matthias P Mayer, Chrisostomos Prodromou & Len Neckers

doi:10.1038/nsmb.1682

Hsp90 is a molecular chaperone essential for the maintenance of cellular homeostasis. Now multiple approaches are used to study the deleterious effects of mutations in -strand 8 of the N domain of Hsp90 and the role of the charged linker between N and M domains in mediating such effects.

Abstract - Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain | Full Text - Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain | PDF (1,500 KB) - Hsp90 charged-linker truncation reverses the functional consequences of weakened hydrophobic contacts in the N domain | Supplementary information

Structural insights into RNA processing by the human RISC-loading complex - pp1148 - 1153

Hong-Wei Wang, Cameron Noland, Bunpote Siridechadilok, David W Taylor, Enbo Ma, Karin Felderer, Jennifer A Doudna & Eva Nogales

doi:10.1038/nsmb.1673

Despite the importance of small RNA–mediated silencing, no structural information exists for complexes of known function. Using single-particle EM, the structure of the minimal functional unit for RNAi in humans (AGO2, Dicer and TRBP) is now presented.

Abstract - Structural insights into RNA processing by the human RISC-loading complex | Full Text - Structural insights into RNA processing by the human RISC-loading complex | PDF (1,097 KB) - Structural insights into RNA processing by the human RISC-loading complex | Supplementary information

Single-molecule analysis of protein-free U2–U6 snRNAs - pp1154 - 1159

Zhuojun Guo, Krishanthi S Karunatilaka & David Rueda

doi:10.1038/nsmb.1672

The U2–U6 snRNA complex is argued to adopt different conformations during splicing. Using single-molecule FRET, the dynamics of an RNA representing U2–U6 are now probed and related to splicing steps through probing of mutations previously linked to this process.

Abstract - Single-molecule analysis of protein-free U2-U6 snRNAs | Full Text - Single-molecule analysis of protein-free U2–U6 snRNAs | PDF (904 KB) - Single-molecule analysis of protein-free U2–U6 snRNAs | Supplementary information

Ago–TNRC6 triggers microRNA-mediated decay by promoting two deadenylation steps - pp1160 - 1166

Chyi-Ying A Chen, Dinghai Zheng, Zhenfang Xia & Ann-Bin Shyu

doi:10.1038/nsmb.1709

miRNAs can repress transcripts through decay. Mammalian miRNA-mediated deadenylation is now shown to involve both the Pan2–Pan3 and the Ccr4–Caf1 deadenylases. Such deadenylation can be triggered by tethered Ago or TNRC6 and is followed by decapping of the reporter.

Abstract - Ago-TNRC6 triggers microRNA-mediated decay by promoting two deadenylation steps | Full Text - Ago–TNRC6 triggers microRNA-mediated decay by promoting two deadenylation steps | PDF (1,061 KB) - Ago–TNRC6 triggers microRNA-mediated decay by promoting two deadenylation steps | Supplementary information

Involvement of a chromatin remodeling complex in damage tolerance during DNA replication - pp1167 - 1172

Karina B Falbo, Constance Alabert, Yuki Katou, Su Wu, Junhong Han, Tammy Wehr, Jing Xiao, Xiangwei He, Zhiguo Zhang, Yang Shi, Katsu Shirahige, Philippe Pasero & Xuetong Shen

doi:10.1038/nsmb.1686

Remodeling complexes can affect DNA transactions by altering chromatin, thus affecting accessibility of DNA. The INO80 remodeling complex has previously been implicated in replication and analyses now argue that it specifically acts through the DNA damage tolerance pathways that resolve recombination intermediates at impeded replication forks.

Abstract - Involvement of a chromatin remodeling complex in damage tolerance during DNA replication | Full Text - Involvement of a chromatin remodeling complex in damage tolerance during DNA replication | PDF (1,174 KB) - Involvement of a chromatin remodeling complex in damage tolerance during DNA replication | Supplementary information

Molecular architecture of the Nup84–Nup145C–Sec13 edge element in the nuclear pore complex lattice - pp1173 - 1177

Stephen G Brohawn & Thomas U Schwartz

doi:10.1038/nsmb.1713

• PDB code

  • 3JRO
  • 3JRP

• 3D view

  • 3JRO
  • 3JRP

The nuclear pore complex (NPC) is key to nucleocytoplasmic transport and is based on a stable scaffold involving multiple heptameric Y complexes. The structure of the Nup84–Nup145C–Sec13 component of the Y complex now indicates that the Nup84–Nup145C and Sec31 homotypic interface in the COPII lattice are analogous, suggesting a lattice NPC model.

Abstract - Molecular architecture of the Nup84-Nup145C-Sec13 edge element in the nuclear pore complex lattice | Full Text - Molecular architecture of the Nup84–Nup145C–Sec13 edge element in the nuclear pore complex lattice | PDF (805 KB) - Molecular architecture of the Nup84–Nup145C–Sec13 edge element in the nuclear pore complex lattice | Supplementary information

Membrane promotes tBID interaction with BCL_XL - pp1178 - 1185

Ana J García-Sáez, Jonas Ries, Mar Orzáez, Enrique Pérez-Payà & Petra Schwille

doi:10.1038/nsmb.1671

Studying protein interactions at membranes is a technical challenge. A quantitative approach to measuring the interaction between the apoptotic proteins tBid and Bcl using fluorescence correlation spectroscopy reveals that membranes have an active role in modulating BCL2 protein interactions.

Abstract - Membrane promotes tBID interaction with BCL: XL | Full Text - Membrane promotes tBID interaction with BCLXL | PDF (1,031 KB) - Membrane promotes tBID interaction with BCLXL | Supplementary information

Structural insight into mammalian sialyltransferases - pp1186 - 1188

Francesco V Rao, Jamie R Rich, Bojana Raki, Sai Buddai, Marc F Schwartz, Karl Johnson, Caryn Bowe, Warren W Wakarchuk, Shawn DeFrees, Stephen G Withers & Natalie C J Strynadka

doi:10.1038/nsmb.1685

• PDB code

  • 2WML
  • 2WNB
  • 2WNF

• 3D view

  • 2WML
  • 2WNB
  • 2WNF

Sialic acid is the most abundant terminal monosaccharide on mammalian cell surface glycoconjugates. The crystal structures of a mammalian sialyltransferase, that of porcine ST3Gal-I, in the apo form and bound to analogues of the donor and acceptor substrate are now described, providing insights into the catalytic mechanism and for inhibitor design.

Abstract - Structural insight into mammalian sialyltransferases | Full Text - Structural insight into mammalian sialyltransferases | PDF (580 KB) - Structural insight into mammalian sialyltransferases | Supplementary information

See also: News and Views by Paulson & Rademacher

Crystal structure of TNF complexed with a poxvirus MHC-related TNF binding protein - pp1189 - 1191

Zhiru Yang, Anthony P West Jr & Pamela J Bjorkman

doi:10.1038/nsmb.1683

• PDB code

  • 3IT8

• 3D view

  • 3IT8

The poxvirus 2L protein binds tumor necrosis factor- (TNF). Structural data now indicate that 2L interacts with TNF at a site overlapping with that for its receptor, arguing for the basis of inhibition of receptor interaction and TNF-induced immune responses.

Abstract - Crystal structure of TNF[alpha] complexed with a poxvirus MHC-related TNF binding protein | Full Text - Crystal structure of TNF complexed with a poxvirus MHC-related TNF binding protein | PDF (683 KB) - Crystal structure of TNF complexed with a poxvirus MHC-related TNF binding protein | Supplementary information

Regulation of a muralytic enzyme by dynamic membrane topology - pp1192 - 1194

Qingan Sun, Gabriel F Kuty, Arulandu Arockiasamy, Min Xu, Ry Young & James C Sacchettini

doi:10.1038/nsmb.1681

• PDB code

  • 3HDE
  • 3HDF

• 3D view

  • 3HDE
  • 3HDF

Phage lysis requires the enzymatic degradation of the host cell wall by a phage-encoded lysin. Secretory endolysins are inactive at the membrane but active in the cytoplasm, and the signal-anchor-release (SAR) domain is shown to be essential for regulating its effects. The structure of coliphage 21 lysozyme explains how this endolysin is controlled.

Abstract - Regulation of a muralytic enzyme by dynamic membrane topology | Full Text - Regulation of a muralytic enzyme by dynamic membrane topology | PDF (737 KB) - Regulation of a muralytic enzyme by dynamic membrane topology | Supplementary information

Positive selection of DNA-protein interactions in mammalian cells through phenotypic coupling with retrovirus production - pp1195 - 1199

Ulrich Tschulena, Kenneth R Peterson, Beatriz Gonzalez, Halyna Fedosyuk & Carlos F Barbas III

doi:10.1038/nsmb.1677

Screening a library of artificial zinc fingers for transcriptional activators in mammalian cells can be laborious. Now a strategy is described that couples the screening to production of retroviral particles that will carry the positive clones, allowing iterative rounds of selection.

Abstract - Positive selection of DNA-protein interactions in mammalian cells through phenotypic coupling with retrovirus production | Full Text - Positive selection of DNA-protein interactions in mammalian cells through phenotypic coupling with retrovirus production | PDF (574 KB) - Positive selection of DNA-protein interactions in mammalian cells through phenotypic coupling with retrovirus production | Supplementary information