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Friday, December 4, 2009

Nature Structural & Molecular Biology Contents: December 2009 Volume #16 pp 1201 - 1331


December 2009 Volume 16 Number 12, pp 1201 - 1331

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Come together, right now p1201
Some bacteria have the remarkable ability to switch from a
free-swimming, planktonic phase to coexistence in a complex
biofilm. In this issue of NSMB, the structures of the ligand-bound
c-di-GMP riboswitch give insight into some of the molecular
processes linked to lifestyle changes but also suggest a potential
avenue for applications that begs exploration.

Warren L. DeLano 21 June 1972-3 November 2009 pp1202 - 1203
Axel T Brunger and James A Wells

Chromosome end protection becomes even more complex pp1205 - 1206
Jan Karlseder
Chromosome end protection is accomplished by telomeres. How cells
cope with spontaneously unprotected telomeres while avoiding cell
cycle arrest or cell death is a fascinating question.

Flu BM2 structure and function pp1207 - 1209
Timothy A Cross
Flu viruses package essential functions into a small integral
membrane protein known as M2. Such small membrane proteins
represent major challenges for structural biology. A new study
presented in this issue details the structure and functions of
the influenza B M2 protein through the use of functional
domain-specific solution NMR spectroscopy.

Ubiquitin linkages make a difference pp1209 - 1210
Ivan Dikic and Volker Dotsch
Ubiquitin chains have critical roles in activating the NF-kappaB
pathway and mediating immune responses. Recent structural work on
distinct ubiquitin chains in complexes with selective
ubiquitin-binding domains provides an explanation for directionality
and specificity in the NF-kappaB pathway.

Research highlights p1211

Recognition of the bacterial second messenger cyclic diguanylate by
its cognate riboswitch pp1212 - 1217
Nadia Kulshina, Nathan J Baird and Adrian R Ferre-D'Amare
c-di-GMP is a bacterial second messenger implicated in processes
such as biofilm formation and switches between motile and sedentary
lifestyles. The structure of the c-di-GMP-binding GEMM riboswitch
is now presented with ligand and the large conformational changes
between ligand-bound and unbound forms analyzed by small-angle
X-ray scattering.

Structural basis of ligand binding by a c-di-GMP riboswitch
pp1218 - 1223
Kathryn D Smith et al.
The GEMM riboswitch is conserved in diverse bacteria and recognizes
the second messenger c-di-GMP which mediates many processes, such
as the transition between sedentary and motile behavior. The
structure of the GEMM riboswitch with ligand now elucidates ligand
recognition and specificity.

Nonspecifically bound proteins spin while diffusing along DNA
pp1224 - 1229
Paul C Blainey et al.
Some proteins move along DNA, searching for a specific target. Now
these proteins are shown to follow a helical path, i.e., they rotate
while sliding, hence maintaining a specific orientation to the DNA
helix. This is accomplished by tracking single molecules of labeled
human oxoguanine DNA glycosylase 1, alone or bound to a bulky
streptavidin moiety, and calculating their diffusion constants.

Structural insights into the mechanism of abscisic acid signaling by
PYL proteins pp1230 - 1236
Ping Yin et al.
PYL-PYR proteins were recently described as receptors for the plant
hormone abscisic acid (ABA) and as inhibitors of the phosphatases
ABI1 and ABI2 in the presence of ABA. The crystal structures of
PYL2 in its apo and ABA-bound forms and of the ternary complex
PYL1-ABA-ABI1 have now been solved, providing insight into ABA
sensing and signaling.

Reconstitution of both steps of Saccharomyces cerevisiae splicing
with purified spliceosomal components pp1237 - 1243
Zbigniew Warkocki et al.
Pre-mRNA splicing is catalyzed by the spliceosome in a two-step
reaction. Both catalytic steps have now been reconstituted using
purified, defined components. This system identifies a role for
Cwc25 in the first step of splicing and allows future detailed
mechanistic analyses of splicing.

Spontaneous occurrence of telomeric DNA damage response in the
absence of chromosome fusions pp1244 - 1251
Anthony J Cesare et al.
Telomeric DNA is protected by the shelterin complex, whose disruption
triggers DNA-damage responses, checkpoint activation and chromosomal
fusions. Now analysis of human cell lines reveals a spontaneously
occurring intermediate state in which the DNA-damage response is
activated at the telomeres without cell cycle arrest or chromosomal
fusions, and with TRF2 playing a central role in determining such a

Physical determinants of strong voltage sensitivity of K+ channel block
pp1252 - 1258
Yanping Xu, Hyeon-Gyu Shin, Szilvia Szep and Zhe Lu
Inward-rectifier K+ channels respond to voltage via blockage by
intracellular polyamines. How these blockers work is not entirely
clear. Now a crystal structure of the cytoplasmic portion of Kir3.1
reveals five ion sites, and functional analyses indicate these ions
are displaced by spermine binding.

Distinct passenger strand and mRNA cleavage activities of human
Argonaute proteins pp1259 - 1266
Bingbing Wang et al.
Argonaute family members are effectors in small RNA-mediated
silencing. In vitro analysis of the four human Argonautes
demonstrates that AGO1 and AGO2 mediate multiple rounds of
microRNA strand dissociation, mediate siRNA passenger-strand
cleavage activity, and indicate distinct mechanisms from mRNA
endonuclease activity.

Solution structure and functional analysis of the influenza B proton channel
pp1267 - 1271
Junfeng Wang, Rafal M Pielak, Mark A McClintock and James J Chou
Influenza B virus is responsible for about half of all the seasonal
flu cases. The integral protein BM2 oligomerizes and forms a
pH-activated proton channel that is essential for viral entry into
host cells. The solution structures of the membrane-embedded chain
domain and the C-terminal cytoplasmic domain reveal significant
differences from the AM2 protein of influenza A virus and explain
antiviral drug resistance.

Mechanism of chromatin remodeling and recovery during passage of RNA
polymerase II pp1272 - 1278
Olga I Kulaeva et al.
On specific DNA sequences in vitro, a nucleosome is a polar barrier
to RNA polymerase II (Pol II). Further analyses of the sequences
underlying this barrier effect now indicate the formation of a loop
that would preserve the position of the nucleosome on the DNA, while
allowing passage of Pol II.

The chaperonin TRiC blocks a huntingtin sequence element that
promotes the conformational switch to aggregation
pp1279 - 1285
Stephen Tam et al.
The eukaryotic group II chaperonin TRiC can block polyQ tract
aggregation, present in proteins such as Htt. Here the TRiC-Htt
interaction is examined using in vitro and in vivo experiments,
revealing that TRiC does not physically block the polyQ tract,
but rather sequesters a short N-terminal sequence that promotes
the amyloidogenic conformation.

An acetylated form of histone H2A.Z regulates chromosome architecture
in Schizosaccharomyces pombe pp1286 - 1293
Hyun-Soo Kim et al.
H2A.Z is implicated in genome stability across species. Acetylation
of this histone variant in S. pombe is now found to be involved in
maintaining condensed chromosomes during mitosis, with premature
dissociation of condensin occurring in its absence.

Basis of substrate binding and conservation of selectivity in the CLC
family of channels and transporters pp1294 - 1301
Alessandra Picollo, Mattia Malvezzi, Jon C D Houtman and Alessio Accardi
The crucial ion-binding events that drive H+/Cl- exchange in the
bacterial transporter CLC-ec1 are now probed by isothermal
calorimetry and detergent-solubilized proteins. The results
indicate that transport via CLC channels have an inherent
directionality, rather than being driven by an electrochemical

The chromosomal association of condensin II is regulated by a
noncatalytic function of PP2A pp1302 - 1308
Ai Takemoto et al.
Condensins are protein complexes essential for eukaryotic mitosis
and whose chromosome association is regulated by phosphorylation
and dephosphorylation events. Now protein phosphatase PP2A is
important for association of condensin II to mitotic chromosomes,
but its catalytic activity is not required.

A stepwise 2'-hydroxyl activation mechanism for the bacterial
transcription termination factor Rho helicase pp1309 - 1316
Annie Schwartz et al.
The bacterial transcriptional termination factor Rho is a hexameric
helicase that tracks along RNA and dissociates DNA-RNA hybrids. Here
the activity of Rho is examined using nucleotide analog interference
mapping, revealing that the helicase takes large, 7-nt steps,
triggered by contacts with 2'OH in the tracked RNA substrate.

Mechanism of potassium-channel selectivity revealed by Na+ and Li+
binding sites within the KcsA pore pp1317 - 1324
Ameer N Thompson et al.
How potassium channels select intracellular K+ over Na+ and Li+ is
investigated, using experimental and theoretical approaches. The
results indicate that selectivity is not due to higher affinity for
K+ binding, but rather to an energy barrier blocking Na+ and Li+
entry in the presence of K+.

IDN1 and IDN2 are required for de novo DNA methylation in Arabidopsis
thaliana pp1325 - 1327
Israel Ausin, Todd C Mockler, Joanne Chory and Steven E Jacobsen
De novo methylation of DNA can affect the function of underlying
genes and transposons in plants. Using a genetic screen, two factors
required for de novo demethylation in Arabidopsis thaliana are
identified and analyzed.

Two-sided ubiquitin binding explains specificity of the TAB2 NZF
domain pp1328 - 1330
Yogesh Kulathu et al.
The TAK1 kinase binds K63-linked ubiquitin specifically via its TAB2
subunit. The structure of the TAB2 NZF domain in complex with
K63-linked ubiquitins now indicates that this domain interacts with
neighboring ubiquitins through distinct sites, explaining the basis
of specific recognition.

Structural and functional studies of the Ras-associating and
pleckstrin-homology domains of Grb10 and Grb14 p1331
Rafael S Depetris, Jinhua Wu and Stevan R Hubbard

Diversity of chemical mechanisms in thioredoxin catalysis revealed by
single-molecule force spectroscopy p1331
Raul Perez-Jimenez et al.

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