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Produced with support from: Novo Nordisk | | | | |  | TABLE OF CONTENTS
| May 2016 Volume 23, Issue 5 |  | | |  |  News and Views
Review
Articles
Brief Communication
Analysis
Corrigendum | | | | | | | Advertisement | | Discovery and technology for human health
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Register for FREE today! |  | | | | | | News and Views |  Top | |  | | α-synuclein folds: the cards are on the table pp359 - 360
Wouter Peelaerts and Veerle Baekelandt
doi:10.1038/nsmb.3209
All current evidence indicates a central role for α-synuclein (α-SYN) amyloid fibrils in Parkinson's disease and other synucleinopathies, but the precise relationship between amyloid aggregates and the resulting phenotype remains poorly understood, partly because of the lack of reliable three-dimensional structures. In this issue, the structure of a toxic α-SYN fibril is now presented at unprecedented resolution.
See also: Article by Tuttle et al. | | | | SIRT6: a new guardian of mitosis pp360 - 362
Barbara Martinez Pastor and Raul Mostoslavsky
doi:10.1038/nsmb.3222
The sirtuin family protein SIRT6 is a stress-responsive NAD-dependent histone deacetylase with key roles in glucose homeostasis, DNA repair and cellular lifespan. SIRT6 is now shown to mediate deacetylation of histone H3 Lys18 specifically at pericentric chromatin, thus maintaining transcriptional silencing of satellite repeats in a manner independent of HP1 and trimethylated H3 Lys9, thereby assuring correct segregation of chromosomes.
See also: Article by Tasselli et al. | | | | Step back for seminal translation pp362 - 363
Shu-Bing Qian
doi:10.1038/nsmb.3217
Translation elongation entails a one-codon movement of the mRNA-tRNA complex along the mRNA and is catalyzed by the forward translocase EF-G. The structurally related back-translocase EF4 catalyzes movement in the opposite direction when the ribosome stalls, but its physiological role in mammals had been unknown. Genetic ablation of EF4 in mice is now found to cause testis-specific mitochondrial deficiency and impaired spermatogenesis.
See also: Article by Gao et al. | | | | A novel regulatory mechanism for the brown-fat uncoupling protein? pp364 - 365
David G Nicholls and Eduardo Rial
doi:10.1038/nsmb.3221
Brown fat has a tremendous capacity to oxidize fatty acids and generate heat, owing to the presence of an 'uncoupling protein', UCP1. The fatty acids themselves are understood to activate UCP1, but Chouchani et al. now propose that oxidation of a critical cysteine residue on UCP1 is additionally required to sensitize the protein to fatty acids. | | | | Cpf1 shape-shifts for streamlined CRISPR cleavage pp365 - 366
Malcolm F White
doi:10.1038/nsmb.3225
Two new studies of the CRISPR nuclease Cpf1 reveal the structural and catalytic flexibility of this leaner, meaner alternative to Cas9. | | | | Translocation: lights, camera, and action pp367 - 368
Xinying Shi and Simpson Joseph
doi:10.1038/nsmb.3219
The fundamental mechanics of how EF-G catalyzes translocation of the mRNA and tRNA pairs on the ribosome has been intensely studied for over three decades. Two kinetic studies now reveal the sequence of events and the timing of key conformational changes in the ribosome during translocation and identify new intermediates in this complex process. | | | | |
| | Review | Top | | | | Regulating the construction and demolition of the synaptonemal complex pp369 - 377
Cori K Cahoon and R Scott Hawley
doi:10.1038/nsmb.3208
The synaptonemal complex (SC) connects homologous chromosomes in meiotic prophase, thus promoting genetic exchange and ensuring accurate chromosomal segregation at anaphase. In this Review, the authors discuss the structural organization of the SC and how its assembly, maintenance and disassembly are regulated in yeast and metazoans. | | Articles | Top | | | | Structural basis for therapeutic inhibition of complement C5 pp378 - 386
Matthijs M Jore, Steven Johnson, Devon Sheppard, Natalie M Barber, Yang I Li, Miles A Nunn, Hans Elmlund & Susan M Lea
doi:10.1038/nsmb.3196
Structural and functional analyses of a new family of tick-derived C5 inhibitors in complex with inhibitor OmCI and therapeutic antibody eculizumab reveal diverse mechanisms for inhibition and provide insight into C5 activation by C5 convertases. | | | | BTG4 is a meiotic cell cycle-coupled maternal-zygotic-transition licensing factor in oocytes pp387 - 394
Chao Yu, Shu-Yan Ji, Qian-Qian Sha, Yujiao Dang, Jian-Jie Zhou, Yin-Li Zhang, Yang Liu, Zhong-Wei Wang, Boqiang Hu, Qing-Yuan Sun, Shao-Chen Sun, Fuchou Tang & Heng-Yu Fan
doi:10.1038/nsmb.3204
B-cell translocation gene-4 (Btg4) bridges interactions of translation initiation factor eIF4E and CCR4-NOT deadenylase, thus triggering decay of maternal mRNA during mouse oocyte maturation. | | | | Structural basis for specific inhibition of Autotaxin by a DNA aptamer pp395 - 401
Kazuki Kato, Hisako Ikeda, Shin Miyakawa, Satoshi Futakawa, Yosuke Nonaka, Masatoshi Fujiwara, Shinichi Okudaira, Kuniyuki Kano, Junken Aoki, Junko Morita, Ryuichiro Ishitani, Hiroshi Nishimasu, Yoshikazu Nakamura & Osamu Nureki
doi:10.1038/nsmb.3200
SELEX selections and crystallographic analyses have allowed development of a DNA aptamer that inhibits autotaxin with high potency and specificity, and exhibits efficacy against bleomycin-induced pulmonary fibrosis in model mice. | | | | Resolving individual steps of Okazaki-fragment maturation at a millisecond timescale pp402 - 408
Joseph L Stodola and Peter M Burgers
doi:10.1038/nsmb.3207
High-resolution kinetic analysis and enzyme trapping assays reveal how PCNA coordinates 5′-flap generation and processing by Pol δ and FEN1 during Okazaki-fragment maturation. | | | | Solid-state NMR structure of a pathogenic fibril of full-length human α-synuclein pp409 - 415
Marcus D Tuttle, Gemma Comellas, Andrew J Nieuwkoop, Dustin J Covell, Deborah A Berthold, Kathryn D Kloepper, Joseph M Courtney, Jae K Kim, Alexander M Barclay, Amy Kendall, William Wan, Gerald Stubbs, Charles D Schwieters, Virginia M Y Lee, Julia M George & Chad M Rienstra
doi:10.1038/nsmb.3194
α-synuclein amyloid fibrils are associated with Parkinson's disease. SSNMR analyses now reveal the atomic structure of a pathogenic human α-synuclein fibril, providing a framework for understanding fibril nucleation, propagation and interactions with small molecules.
See also: News and Views by Peelaerts & Baekelandt | | | | Molecular basis of caspase-1 polymerization and its inhibition by a new capping mechanism pp416 - 425
Alvin Lu, Yang Li, Florian I Schmidt, Qian Yin, Shuobing Chen, Tian-Min Fu, Alexander B Tong, Hidde L Ploegh, Youdong Mao & Hao Wu
doi:10.1038/nsmb.3199
The CARD-only protein INCA inhibits inflammasome assembly by capping caspase-1 CARD oligomers and preventing their further polymerization. | | | | Structures of human ADAR2 bound to dsRNA reveal base-flipping mechanism and basis for site selectivity pp426 - 433
Melissa M Matthews, Justin M Thomas, Yuxuan Zheng, Kiet Tran, Kelly J Phelps, Anna I Scott, Jocelyn Havel, Andrew J Fisher & Peter A Beal
doi:10.1038/nsmb.3203
Crystal structures of the human ADAR2 deaminase domain in complex with RNA duplexes reveal the mechanisms for ADAR2's action and explain its substrate preference. The work also provides a rationale to understand disease-related mutations. | | | | SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence pp434 - 440
Luisa Tasselli, Yuanxin Xi, Wei Zheng, Ruth I Tennen, Zaneta Odrowaz,Federica Simeoni, Wei Li & Katrin F Chua
doi:10.1038/nsmb.3202
The sirtuin family protein SIRT6 maintains pericentric heterochromatin silencing at human centromeres through deacetylation of a newly discovered substrate, H3K18, thus protecting cells against mitotic errors, genomic instability and cellular senescence.
See also: News and Views by Pastor & Mostoslavsky | | | | Mammalian elongation factor 4 regulates mitochondrial translation essential for spermatogenesis pp441 - 449
Yanyan Gao, Xiufeng Bai, Dejiu Zhang, Chunsheng Han, Jing Yuan, Wenbin Liu, Xintao Cao, Zilei Chen, Fugen Shangguan, Zhenyuan Zhu, Fei Gao & Yan Qin
doi:10.1038/nsmb.3206
Genetic ablation of EF4 in mice leads to male sterility due to mitochondrial translation defects, which can be compensated for in somatic tissues by mTOR-mediated upregulation of cytoplasmic translation.
See also: News and Views by Qian | | | | Expansion of antisense lncRNA transcriptomes in budding yeast species since the loss of RNAi pp450 - 455
Eric A Alcid and Toshio Tsukiyama
doi:10.1038/nsmb.3192
RNA interference constrains antisense lncRNA transcriptomes, and its loss during budding yeast evolution is associated with an increase in genome-wide expression of antisense lncRNAs. | | Brief Communication | Top | | | | Zika virus NS1 structure reveals diversity of electrostatic surfaces among flaviviruses pp456 - 458
Hao Song, Jianxun Qi, Joel Haywood, Yi Shi and George F Gao
doi:10.1038/nsmb.3213
The crystal structure of the C-terminal region of Zika virus nonstructural protein 1 (NS1) reveals a fold similar to those of other flaviviruses (dengue and West Nile viruses) but different surface electrostatic features. | | Analysis | Top | | | | Universality of supersaturation in protein-fiber formation pp459 - 461
Troy Cellmer, Frank A Ferrone and William A Eaton
doi:10.1038/nsmb.3197
An analysis of previously published data on fiber formation by sickle-cell hemoglobin reveals a universal curve when delay time is plotted against supersaturation (ratio of protein concentration to solubility). | | Corrigendum | Top | | | | Corrigendum: Structure of a prokaryotic fumarate transporter reveals the architecture of the SLC26 family p462
Eric R Geertsma, Yung-Ning Chang, Farooque R Shaik, Yvonne Neldner, Els Pardon, Jan Steyaert & Raimund Dutzler
doi:10.1038/nsmb0516-462 | | | Top | | | | Advertisement | | Nature Partner Journals: a new home for your research
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