Nature Structural & Molecular Biology Contents: 2017 Volume #24 pp 1 - 96

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January 2017 Volume 24, Issue 1

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Meeting Report


The diverse roles of Hsp90 and where to find them   pp1 - 4
Patricija Van Oosten-Hawle, Daniel N A Bolon and Paul LaPointe
The Eighth International Conference on the Hsp90 Chaperone Machine took place in November 2016 at the Seeon Abbey in Germany. This year's program focused on a variety of topics, reflecting Hsp90's diverse roles in cellular and physiological function. The highlights included structural insights into the Hsp90 folding mechanism and conformational dynamics, post-translational modifications, client protein maturation, Hsp90 cochaperone function and Hsp90's role in disease physiology.

News and Views


New pieces to an old puzzle: identifying the warfarin-binding site that prevents clotting   pp5 - 6
Jacob K Hilton and Wade D Van Horn
Warfarin has been the most widely prescribed anticoagulant for decades. It functions by inhibiting the membrane enzyme vitamin K epoxide reductase (VKOR), but the molecular details of this effect have remained elusive. Two new studies shed light on the warfarin-VKOR interaction. The work has implications for precision medicine and could guide drug discovery.

See also: Article by Shen et al. | Article by Czogalla et al.

Functional RNA classes: a matter of time?   pp7 - 8
Oscar C Bedoya-Reina and Chris P Ponting
Little is known about the functions of long noncoding RNAs compared with the amount of accumulated knowledge concerning protein-mediated mechanisms. A report now proposes a novel RNA classification based on similar kinetics of RNA synthesis, processing and turnover, and the authors predict that RNAs within each class might share functional properties.

See also: Resource by Mukherjee et al.

Single-virus tracking uncovers the missing link between HIV integration site location and viral gene expression   pp8 - 11
Angela Ciuffi, Sara Cristinelli and Sylvie Rato
The site of HIV genome integration is likely a contributing factor in viral gene expression, but such context-specific effects are difficult to demonstrate at the population level. A new approach overcomes this obstacle by tracking individual, barcoded viruses to investigate the relationship between integration site location and the corresponding viral transcription, thereby providing insights essential for understanding HIV production, latency and reactivation.

See also: Article by Chen et al.

Break-induced replication: an unhealthy choice for stress relief?   pp11 - 12
Juraj Kramara, Beth Osia and Anna Malkova
Determining the molecular mechanisms responsible for trinucleotide DNA repeat expansions is critical, as such expansions underlie many neuromuscular and neurodegenerative disorders. Mirkin and colleagues now propose that large-scale expansions of trinucleotide repeats can be generated by DNA-break-induced replication.

See also: Article by Kim et al.

CFTR structure: lassoing cystic fibrosis   pp13 - 14
Bob Ford
Loss of function of the CFTR anion channel leads to cystic fibrosis, the most common inherited condition in humans of European origin. A recently reported structure for CFTR at 3.7-Å resolution reveals an unexpected 'lasso' domain and provides new insights into channel function in healthy individuals and in people with cystic fibrosis.

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Reciprocal regulation of carbon monoxide metabolism and the circadian clock   pp15 - 22
Roman Klemz, Silke Reischl, Thomas Wallach, Nicole Witte, Karsten Jurchott et al.
Genetic and biochemical assays reveal that carbon monoxide produced by heme catabolism influences circadian rhythm in mammals by altering the activity of transcription factor CLOCK-BMAL1 at clock-gene targets.

FICD acts bifunctionally to AMPylate and de-AMPylate the endoplasmic reticulum chaperone BiP   pp23 - 29
Steffen Preissler, Claudia Rato, Luke A Perera, Vladimir Saudek and David Ron
The enzyme FICD was previously known to AMPylate the ER-resident chaperone BiP, inactivating the chaperone. Mammalian FICD is now shown to catalyze the removal of the AMP group from BiP.

A balance between elongation and trimming regulates telomere stability in stem cells   pp30 - 39
Teresa Rivera, Candy Haggblom, Sandro Cosconati and Jan Karlseder
New data reveal that telomere length is maintained in human pluripotent stem cells through the opposing activities of telomerase-meditated elongation and telomere trimming mechanisms promoted by HR factors.

Cryo-EM structures of human RAD51 recombinase filaments during catalysis of DNA-strand exchange   pp40 - 46
Jingfei Xu, Lingyun Zhao, Yuanyuan Xu, Weixing Zhao, Patrick Sung et al.
Cryo-EM analysis captures three states of the human Rad51 recombinase and visualizes structures of presynaptic and postsynaptic filaments as well as a synaptic complex in the process of DNA-strand exchange.

Position effects influence HIV latency reversal   pp47 - 54
Heng-Chang Chen, Javier P Martinez, Eduard Zorita, Andreas Meyerhans and Guillaume J Filion
Barcoded HIV ensembles (B-HIVE) provides a new approach to map HIV integration sites and to determine how genomic context influences proviral transcription activity and response to latency-reversing agents.

See also: News and Views by Ciuffi et al.

The role of break-induced replication in large-scale expansions of (CAG)n/(CTG)n repeats   pp55 - 60
Jane C Kim, Samantha T Harris, Teresa Dinter, Kartik A Shah and Sergei M Mirkin
A newly developed assay in yeast reveals that large-scale expansions of trinucleotide repeats can occur in a single step, rather than through several small-scale events.

See also: News and Views by Kramara et al.

Position-dependent termination and widespread obligatory frameshifting in Euplotes translation   pp61 - 68
Alexei V Lobanov, Stephen M Heaphy, Anton A Turanov, Maxim V Gerashchenko, Sandra Pucciarelli et al.
Large-scale sequencing approaches reveal that the genetic code of Euplotes ciliates supports widespread ribosomal frameshifting at stop codons, and that additional mechanisms are required for efficient translation termination.

Warfarin traps human vitamin K epoxide reductase in an intermediate state during electron transfer   pp69 - 76
Guomin Shen, Weidong Cui, Hao Zhang, Fengbo Zhou, Wei Huang et al.
Mass spectrometry and biochemical analyses reveal that the major form of VKOR found in cells features a disulfide bond between Cys51 and Cys132, and this intermediate is the target of the anticoagulant drug warfarin.

See also: News and Views by Hilton & Van Horn

Warfarin and vitamin K compete for binding to Phe55 in human VKOR   pp77 - 85
Katrin J Czogalla, Arijit Biswas, Klara Honing, Veit Hornung, Kerstin Liphardt et al.
The binding sites for the anticoagulant drug warfarin and for vitamin K on the human VKOR are determined through biochemistry and computational approaches. The results indicate a competitive mechanism of inhibition of VKOR by warfarin.

See also: News and Views by Hilton & Van Horn



Integrative classification of human coding and noncoding genes through RNA metabolism profiles   pp86 - 96
Neelanjan Mukherjee, Lorenzo Calviello, Antje Hirsekorn, Stefano de Pretis, Mattia Pelizzola et al.
Quantitative assessment of transcription, splicing, degradation, localization and translation of coding and noncoding genes allows classification of RNAs on the basis of their metabolism and may aid in inference of lncRNA function.

See also: News and Views by Bedoya-Reina & Ponting

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