World Stem Cell Summit 2010

Wednesday, November 4, 2009

Nature Structural & Molecular Biology Contents: November 2009 Volume #16 pp 1117 - 1199


November 2009 Volume 16 Number 11, pp 1117 - 1199

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Nature Reviews Molecular Cell Biology
Article Series on Cytoskeletal Motors

From October 2009, Nature Reviews Molecular Cell Biology will be
publishing a Series of specially commissioned articles on cytoskeletal
motors. These articles will highlight the progress made in understanding
the mechanics and functions of different types of cytoskeletal motors,
discuss their important roles in cell division, cell motility,
intracellular trafficking and other cellular processes, and report
new approaches to study these molecules.

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Awards season is upon us... p1117
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.

How do transcription factors select specific binding sites in the
genome? pp1118 - 1120
Yongping Pan, Chung-Jung Tsai, Buyong Ma and Ruth Nussinov
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.

Glycan terminator pp1121 - 1122
James C Paulson and Christoph Rademacher
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.

Tracking rates of transcription and splicing in vivo pp1123 - 1124
M Behfar Ardehali and John T Lis
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.

A more structured metabolome pp1125 - 1126
Matthew J Betts and Robert B Russell
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.

Research highlights p1127

Rates of in situ transcription and splicing in large human genes
pp1128 - 1133
Jarnail Singh and Richard A Padgett
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.

A two-pronged strategy to suppress host protein synthesis by SARS
coronavirus Nsp1 protein pp1134 - 1140
Wataru Kamitani et al.
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.

Hsp90 charged-linker truncation reverses the functional consequences
of weakened hydrophobic contacts in the N domain pp1141 - 1147
Shinji Tsutsumi et al.
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 beta-strand 8 of the N
domain of Hsp90 and the role of the charged linker between N and M
domains in mediating such effects.

Structural insights into RNA processing by the human RISC-loading complex
pp1148 - 1153
Hong-Wei Wang et al.
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.

Single-molecule analysis of protein-free U2-U6 snRNAs pp1154 - 1159
Zhuojun Guo, Krishanthi S Karunatilaka and David Rueda
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.

Ago-TNRC6 triggers microRNA-mediated decay by promoting two
deadenylation steps pp1160 - 1166
Chyi-Ying A Chen, Dinghai Zheng, Zhenfang Xia and Ann-Bin Shyu
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.

Involvement of a chromatin remodeling complex in damage tolerance
during DNA replication pp1167 - 1172
Karina B Falbo et al.
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.

Molecular architecture of the Nup84-Nup145C-Sec13 edge element in the
nuclear pore complex lattice pp1173 - 1177
Stephen G Brohawn and Thomas U Schwartz
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.

Membrane promotes tBID interaction with BCLXL pp1178 - 1185
Ana J Garcia-Saez et al.
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.

Structural insight into mammalian sialyltransferases pp1186 - 1188
Francesco V Rao et al.
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

Crystal structure of TNFalpha complexed with a poxvirus MHC-related
TNF binding protein pp1189 - 1191
Zhiru Yang, Anthony P West, Jr and Pamela J Bjorkman
The poxvirus 2L protein binds tumor necrosis factor-alpha (TNFalpha).
Structural data now indicate that 2L interacts with TNFalpha at a
site overlapping with that for its receptor, arguing for the basis
of inhibition of receptor interaction and TNFalpha-induced immune

Regulation of a muralytic enzyme by dynamic membrane topology
pp1192 - 1194
Qingan Sun et al.
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.

Positive selection of DNA-protein interactions in mammalian cells
through phenotypic coupling with retrovirus production pp1195 - 1199
Ulrich Tschulena et al.

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