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| |  | TABLE OF CONTENTS
| October 2011 Volume 18, Issue 10 |  | | |  |  Research Highlights
Articles
Brief Communications
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Which prominent NMR scientist recently won an Agilent Foundation Thought Leader Award to develop improved protein NMR methods? To uncover his identity and hear what he has to say about the award, visit Agilent's NMR and MRI blog www.SPINSIGHTS.net |
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| | | | Advertisement | | Nature Cell Biology
Focus on Cell cycle and DNA damage
The maintenance of genomic integrity requires tight control of the cell division process as well as accurate repair of damaged DNA, and failure in such mechanisms can cause developmental disorders and cancer. In the October issue of Nature Cell Biology, leading scientists highlight and discuss new developments in these areas.
Access the Focus online:
www.nature.com/ncb/webfocus/cellcycle |
| | | | Research Highlights |  Top | |  | | Nucleoid organization | Sense after shifting | Signaling through chromatin
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| | | | Articles | Top | | | | Structural analysis of the interaction between Hsp90 and the tumor suppressor protein p53 pp1086 - 1093
Franz Hagn, Stephan Lagleder, Marco Retzlaff, Julia Rohrberg, Oliver Demmer, Klaus Richter, Johannes Buchner and Horst Kessler
doi:10.1038/nsmb.2114
Hsp90 is a molecular chaperone with a wide array of client proteins, including the tumor suppressor p53. Now the structure and interaction of p53 DNA-binding domain with full-length Hsp90 or Hsp90 fragments have been studied by NMR and other biophysical methods. The results indicate that p53 interacts with multiple domains of Hsp90 and adopts a native-like state.
Abstract | Full Text | PDF
| | | | Competition between ADAR and RNAi pathways for an extensive class of RNA targets pp1094 - 1101
Diane Wu, Ayelet T Lamm and Andrew Z Fire
doi:10.1038/nsmb.2129
ADARs deaminate adenosines to inosines in double-stranded RNA (dsRNA). Interestingly, effects seen when ADARs are knocked out can be suppressed by additional knockout of RNAi machinery, suggesting competition between the two pathways. Genome-wide identification of ADAR targets shows that ADAR edits heavily in regions that generate siRNAs when ADAR is absent, indicating a role for ADAR in regulating dsRNA accumulation and thus siRNA production.
Abstract | Full Text | PDF
| | | | Correlated structural kinetics and retarded solvent dynamics at the metalloprotease active site pp1102 - 1108
Moran Grossman, Benjamin Born, Matthias Heyden, Dmitry Tworowski, Gregg B Fields, Irit Sagi and Martina Havenith
doi:10.1038/nsmb.2120
Solvent dynamics are an often overlooked component in enzymatic activity. Terahertz spectroscopy, X-ray absorption analysis and molecular dynamics simulations show that solvent movement is tightly correlated with formation of a productive enzyme–substrate complex, but not an enzyme–inhibitor complex, in a metalloprotease, indicating that solvent motions may assist catalysis.
Abstract | Full Text | PDF
| | | | Structure of collagenase G reveals a chew-and-digest mechanism of bacterial collagenolysis pp1109 - 1114
Ulrich Eckhard, Esther Schönauer, Dorota Nüss and Hans Brandstetter
doi:10.1038/nsmb.2127
Collagen is highly abundant in the biosphere but is not easily degraded by proteases. The crystal structure of Clostridium histolyticum collagenase G reveals a pathway of recognition, unraveling and degradation for collagen breakdown.
Abstract | Full Text | PDF
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| | Spliceosome assembly is coupled to RNA polymerase II dynamics at the 3′ end of human genes pp1115 - 1123
Sandra Bento Martins, José Rino, Teresa Carvalho, Célia Carvalho, Minoru Yoshida, Jasmim Mona Klose, Sérgio Fernandes de Almeida and Maria Carmo-Fonseca
doi:10.1038/nsmb.2124
Post-transcriptional maturation of pre-mRNAs involves a number of processes that are now known to interact with transcription itself. Mutations affecting early spliceosome assembly, but not a drug targeting a catalytic step of splicing, are now shown to lead to nascent transcript retention and pausing of RNA polymerase II predominantly at the 3′ end of the gene, suggesting cross-talk between splicing and transcriptional termination.
Abstract | Full Text | PDF
| | | | The Rad50 coiled-coil domain is indispensable for Mre11 complex functions pp1124 - 1131
Marcel Hohl, Youngho Kwon, Sandra Muñoz Galván, Xiaoyu Xue, Cristina Tous, Andrés Aguilera, Patrick Sung and John H J Petrini
doi:10.1038/nsmb.2116
Rad50 is part of the Mre11 complex, which plays a central role in DNA damage response and repair. Rad50 has a long coiled-coil region that links its globular DNA-binding domain and hook. Now the role of this region is tested by a series of truncations and functional analyses, which reveal that the HR and NHEJ functions of the Mre11 can be separated.
Abstract | Full Text | PDF
| | | | Defects in RNA quality control factors reveal RNAi-independent nucleation of heterochromatin pp1132 - 1138
Francisca E Reyes-Turcu, Ke Zhang, Martin Zofall, Eesin Chen and Shiv I S Grewal
doi:10.1038/nsmb.2122
Previous analyses have indicated that heterochromatin assembly in Schizosaccharomyces pombe involves an RNAi-mediated mechanism. Analyses aimed at elucidating the targeting of heterochromatin at centromeres now show that RNAi-independent mechanisms exist that also exploit transcription and non-coding RNAs to promote heterochromatin formation.
Abstract | Full Text | PDF
| | | | Weak seed-pairing stability and high target-site abundance decrease the proficiency of lsy-6 and other microRNAs pp1139 - 1146
David M Garcia, Daehyun Baek, Chanseok Shin, George W Bell, Andrew Grimson and David P Bartel
doi:10.1038/nsmb.2115
A single miRNA can target hundreds of distinct transcripts, but some miRNAs such as C. elegans lsy-6 have very low target proficiency. The reasons behind this are now identified as weak seed-pairing stability and high target-site abundance. These findings have implications for understanding off-target effects of siRNAs and improving miRNA target predictions.
Abstract | Full Text | PDF
| | | | Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant α-1 antitrypsin from the endoplasmic reticulum pp1147 - 1152
Ethan J Greenblatt, James A Olzmann and Ron R Kopito
doi:10.1038/nsmb.2111
Endoplasmic reticulum-associated degradation (ERAD) substrates must be dislocated across the ER membrane through a process driven by the ATPase p97/VCP, and Derlins are thought to be part of the dislocation machinery. New data identify Derlin-1 as an inactive member of the rhomboid family that facilitates the release of ERAD substrates from the ER, following their transfer across the membrane.
Abstract | Full Text | PDF
| | | | Recognition of the pre-miRNA structure by Drosophila Dicer-1 pp1153 - 1158
Akihisa Tsutsumi, Tomoko Kawamata, Natsuko Izumi, Hervé Seitz and Yukihide Tomari
doi:10.1038/nsmb.2125
It has been unclear how fly Dicer-1 exclusively recognizes pre-miRNAs. New analyses show that fly Dicer-1 recognizes the single-stranded terminal loop structure of pre-miRNAs through its N-terminal helicase domain, checks the loop size and measures the distance between the 3′ overhang and the terminal loop. This unique mechanism allows fly Dicer-1 to inspect the authenticity of pre-miRNA structures.
Abstract | Full Text | PDF
| | | | Protonation of key acidic residues is critical for the K+-selectivity of the Na/K pump pp1159 - 1163
Haibo Yu, Ian M Ratheal, Pablo Artigas and Benoît Roux
doi:10.1038/nsmb.2113
For each ATP molecule, the Na/K pump extrudes three Na+ and imports two K+ ions by alternating between outward- and inward-facing conformations that preferentially bind K+ or Na+, respectively. Molecular dynamics simulations based on atomic models, together with electrophysiological experiments, show that protonation of several acidic residues that form the cation-binding sites is crucial to achieve K+ selectivity.
Abstract | Full Text | PDF
| | | | The export factor Yra1 modulates mRNA 3′ end processing pp1164 - 1171
Sara A Johnson, Hyunmin Kim, Benjamin Erickson and David L Bentley
doi:10.1038/nsmb.2126
Yra1 is an export factor known to link 3′ end formation of mRNAs to export through interaction with Pcf11, a subunit of the cleavage-polyadenylation factor CF1A. Yra1 is now found to regulate assembly of CF1A and affect poly(A) site choice.
Abstract | Full Text | PDF
| | Brief Communications | Top | | | | Apo and InsP3-bound crystal structures of the ligand-binding domain of an InsP3 receptor pp1172 - 1174
Chun-Chi Lin, Kyuwon Baek and Zhe Lu
doi:10.1038/nsmb.2112
Inositol 1,4,5-triphosphate (InsP3) receptors are ligand-activated calcium channels in the endoplasmic reticulum membrane, and they are responsible for the cytoplasmic Ca2+ efflux that triggers many cellular processes. The crystal structures of the ligand-binding domain of rat type I InsP3R in its apo and ligand-bound form reveal the conformational changes that ultimately control channel gating.
First paragraph | Full Text | PDF
| | | | Crystal structure of a monomeric retroviral protease solved by protein folding game players pp1175 - 1177
Firas Khatib, Frank DiMaio, Foldit Contenders Group, Foldit Void Crushers Group, Seth Cooper, Maciej Kazmierczyk, Miroslaw Gilski, Szymon Krzywda, Helena Zabranska, Iva Pichova, James Thompson, Zoran Popović, Mariusz Jaskolski and David Baker
doi:10.1038/nsmb.2119
The online game Foldit invites players to solve problems involving protein structure prediction. Now Foldit players have been recruited to work on a modeling problem and ultimately solve the crystal structure of a retroviral protease that had resisted previous determination.
First paragraph | Full Text | PDF
| | | Top | | | | Advertisement | | Nature Reviews Molecular Cell Biology
FOCUS ON MORPHOGENESIS
Cells in a developing organism reorganize to allow tissues and organs to take their shape through morphogenesis. In this focus issue, specially commissioned articles highlight how our cell biological understanding of morphogenesis is gaining new ground and consider the implications for tissue homeostasis and disease.
Read the Focus online:
www.nature.com/nrm/focus/morphogenesis |
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