Table of contents
December 2008, Volume 15 No 12 pp1233-1351
About the coverEditorial
World AIDS Day 2008 - p1233
doi:10.1038/nsmb1208-1233
NSMB observes World AIDS Day by reflecting on the crucial role of basic research in fighting this epidemic.
Full Text - World AIDS Day 2008 | PDF (221 KB) - World AIDS Day 2008
News and Views
The importance of presentation - pp1234 - 1235
Anthony R Clarke
doi:10.1038/nsmb1208-1234
Analysis of in vivo and in vitro interactions between chaperonins and the whole spectrum of potential cytoplasmic substrates helps answer the vexed question of substrate specificity in the TRiC system.
Full Text - The importance of presentation | PDF (321 KB) - The importance of presentation
See also: Article by Yam et al.
Is the spliceosome a ribonucleoprotein enzyme? - pp1235 - 1237
John Abelson
doi:10.1038/nsmb1208-1235
New work suggests that Prp8, a highly conserved protein in the heart of the spliceosome, both orients the substrate and participates in catalysis.
Full Text - Is the spliceosome a ribonucleoprotein enzyme? | PDF (430 KB) - Is the spliceosome a ribonucleoprotein enzyme?
The N-end rule at atomic resolution - pp1238 - 1240
Alexander Varshavsky
doi:10.1038/nsmb1208-1238
The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. The N-end rule pathway, ubiquitin-dependent in eukaryotes, is also present in prokaryotes, which lack the ubiquitin system. An illuminating new study presents the crystal structure of a bacterial N-end rule recognition component in complex with a peptide containing a cognate degradation signal.
Full Text - The N-end rule at atomic resolution | PDF (226 KB) - The N-end rule at atomic resolution
When loose ends finally meet - pp1241 - 1242
Michael S Y Huen & Junjie Chen
doi:10.1038/nsmb1208-1241
The tumor suppressor protein 53BP1 decorates DNA damage sites and is instrumental for nonhomologous end joining. Evidence that 53BP1 facilitates synapsis of DNA ends by modulating chromatin dynamics reveals a hitherto unanticipated strategy for joining distant ends.
Full Text - When loose ends finally meet | PDF (204 KB) - When loose ends finally meet
PARP: a transferase by any other name - pp1243 - 1244
Susanne Till, Konstantina Diamantara & Andreas G Ladurner
doi:10.1038/nsmb1208-1243
A recent report shows that several 'poly-ADP-ribose-polymerases' may function exclusively as a family of endogenous mono-ADP-ribosyltransferases, providing a new, molecularly less complex and broadened cellular role for this elusive post-translational modification.
Full Text - PARP: a transferase by any other name | PDF (342 KB) - PARP: a transferase by any other name
Research Highlights
Research highlights - p1245
Inês Chen, Maria Hodges & Sabbi Lall
doi:10.1038/nsmb1208-1245
Full Text - Research highlights | PDF (180 KB) - Research highlights
Articles
Bach1 inhibits oxidative stress–induced cellular senescence by impeding p53 function on chromatin - pp1246 - 1254
Yoshihiro Dohi, Tsuyoshi Ikura, Yutaka Hoshikawa, Yasutake Katoh, Kazushige Ota, Ayako Nakanome, Akihiko Muto, Shinji Omura, Tsutomu Ohta, Akihiro Ito, Minoru Yoshida, Tetsuo Noda & Kazuhiko Igarashi
doi:10.1038/nsmb.1516
Oxidative stress can lead to cellular senescence, in a p53-dependent pathway. Bach1, a transcription factor that regulates the response to oxidative stress, is now shown to inhibit senescence induced by high oxygen concentrations or by Ras. Bach1 is recruited to a subset of p53 target genes and contributed to impeding p53 action by promoting histone deacetylation.
Abstract - | Full Text - Bach1 inhibits oxidative stress–induced cellular senescence by impeding p53 function on chromatin | PDF (852 KB) - Bach1 inhibits oxidative stress–induced cellular senescence by impeding p53 function on chromatin | Supplementary information
Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies - pp1255 - 1262
Alice Y Yam, Yu Xia, Hen-Tzu Jill Lin, Alma Burlingame, Mark Gerstein & Judith Frydman
doi:10.1038/nsmb.1515
The interactome of eukaryotic chaperonin TRiC/CCT is identified through a genome-wide approach, revealing an enrichment in large, multidomain proteins, or components of multimeric complexes, rich in hydrophobic sequences and with high 
-sheet propensity. Thus, TRiC substrates are slow-folding proteins with complex topology, which are likely to be more prone to aggregation.
Abstract - | Full Text - Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies | PDF (1,298 KB) - Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies | Supplementary information
See also: News and Views by Clarke
Single-RNA counting reveals alternative modes of gene expression in yeast - pp1263 - 1271
Daniel Zenklusen, Daniel R Larson & Robert H Singer
doi:10.1038/nsmb.1514
Understanding the kinetics of gene expression involves accurate quantitation of gene expression. This is now undertaken by quantifying nascent-RNA levels and relating this indication of transcriptional activity to mRNA abundance in single yeast cells. Combining these measurements with computational modeling indicates that the tested yeast housekeeping genes are probably expressed through single initiation events, whereas a SAGA-transcribed gene shows behavior consistent with transcriptional bursting.
Abstract - | Full Text - Single-RNA counting reveals alternative modes of gene expression in yeast | PDF (3,659 KB) - Single-RNA counting reveals alternative modes of gene expression in yeast | Supplementary information
Structure of a RSC–nucleosome complex and insights into chromatin remodeling - pp1272 - 1277
Yuriy Chaban, Chukwudi Ezeokonkwo, Wen-Hsiang Chung, Fan Zhang, Roger D Kornberg, Barbara Maier-Davis, Yahli Lorch & Francisco J Asturias
doi:10.1038/nsmb.1524
The ATP-dependent chromatin-remodeling complexes are involved in repositioning, evicting and restructuring nucleosomes. The EM reconstruction of the RSC remodeler in complex with a nucleosome gives structural insights into remodeling.
Abstract - | Full Text - Structure of a RSC–nucleosome complex and insights into chromatin remodeling | PDF (694 KB) - Structure of a RSC–nucleosome complex and insights into chromatin remodeling | Supplementary information
Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B - pp1278 - 1286
Dong Yang, Neggy Rismanchi, Benoît Renvoisé, Jennifer Lippincott-Schwartz, Craig Blackstone & James H Hurley
doi:10.1038/nsmb.1512
PDB code
3D view
Emerging evidence suggests that ESCRT proteins, well characterized in their role in multivesicular body trafficking, contribute to various cellular processes including cytokinesis. Structural and functional analyses indicate that the ESCRT-III protein CHMP1B promotes the midbody localization of spastin, a microtubule-severing protein required for membrane abscission.
Abstract - | Full Text - Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B | PDF (1,067 KB) - Structural basis for midbody targeting of spastin by the ESCRT-III protein CHMP1B | Supplementary information
Structural insights into the Cyclin T1–Tat–TAR RNA transcription activation complex from EIAV - pp1287 - 1292
Kanchan Anand, Antje Schulte, Karin Vogel-Bachmayr, Klaus Scheffzek & Matthias Geyer
doi:10.1038/nsmb.1513
PDB code
3D view
The replication of many retroviruses depends on interactions between the viral TAR RNA element and Tat as well as Cyclin T1, a component of the cellular transcriptional elongation complex. Structural insights into this ternary complex now suggest that the equine infectious anemia virus TAR is engaged by both proteins with Tat in a helical conformation and that binding depends on flipping out specific bases in the TAR loop region.
Abstract - | Full Text - Structural insights into the Cyclin T1–Tat–TAR RNA transcription activation complex from EIAV | PDF (839 KB) - Structural insights into the Cyclin T1–Tat–TAR RNA transcription activation complex from EIAV | Supplementary information
Structure of the Shigella T3SS effector IpaH defines a new class of E3 ubiquitin ligases - pp1293 - 1301
Alexander U Singer, John R Rohde, Robert Lam, Tatiana Skarina, Olga Kagan, Rosa DiLeo, Nickolay Y Chirgadze, Marianne E Cuff, Andrzej Joachimiak, Mike Tyers, Philippe J Sansonetti, Claude Parsot & Alexei Savchenko
doi:10.1038/nsmb.1511
PDB code
3D view
The IpaH family of Shigella virulence factors are E3 ubiquitin ligases that may target host proteins. Structural and functional characterization of IpaH1.4 and IpaH9.8 reveal a unique C-terminal catalytic domain that seems to have HECT-like E3 ligase activity. Together with an accompanying publication from Zhu et al., these data suggest that the IpaH proteins constitute a new category of ubiquitin ligases.
Abstract - | Full Text - Structure of the Shigella T3SS effector IpaH defines a new class of E3 ubiquitin ligases | PDF (1,284 KB) - Structure of the Shigella T3SS effector IpaH defines a new class of E3 ubiquitin ligases | Supplementary information
Structure of a Shigella effector reveals a new class of ubiquitin ligases - pp1302 - 1308
Yongqun Zhu, Hongtao Li, Liyan Hu, Jiayi Wang, Yan Zhou, Zhimin Pang, Liping Liu & Feng Shao
doi:10.1038/nsmb.1517
PDB code
3D view
The IpaH proteins from Shigella show ubiquitin-ligase activity but lack obvious sequence similarity to HECT- or RING-type ubiquitin ligases. The crystal structure of IpaH3 reveals a two-domain protein with HECT-like catalytic activity mapped to a C-terminal domain of novel fold. These findings suggest that IpaH proteins represent a new family of ubiquitin ligases, a conclusion supported by results from a related study by Tyers et al.
Abstract - | Full Text - Structure of a Shigella effector reveals a new class of ubiquitin ligases | PDF (721 KB) - Structure of a Shigella effector reveals a new class of ubiquitin ligases | Supplementary information
Structural basis of nucleotide exchange and client binding by the Hsp70 cochaperone Bag2 - pp1309 - 1317
Zhen Xu, Richard C Page, Michelle M Gomes, Ekta Kohli, Jay C Nix, Andrew B Herr, Cam Patterson & Saurav Misra
doi:10.1038/nsmb.1518
Bag2 acts as a nucleotide-exchange factor for Hsp70 and also binds misfolded substrates. Now structural work reveals that Bag2 promotes nucleotide exchange via a mechanism distinct from other Hsp70 nucleotide-exchange factors, and mapping of the binding sites for client peptides suggests how Bag2 assists Hsp70 in processing misfolded proteins.
Abstract - | Full Text - Structural basis of nucleotide exchange and client binding by the Hsp70 cochaperone Bag2 | PDF (1,063 KB) - Structural basis of nucleotide exchange and client binding by the Hsp70 cochaperone Bag2 | Supplementary information
The MSL3 chromodomain directs a key targeting step for dosage compensation of the Drosophila melanogaster X chromosome - pp1318 - 1325
Tuba H Sural, Shouyong Peng, Bing Li, Jerry L Workman, Peter J Park & Mitzi I Kuroda
doi:10.1038/nsmb.1520
The MSL complex is involved in upregulation of genes on the Drosophila melanogaster male X chromosome during dosage compensation. Using mutagenesis, the MSL3 chromodomain is now shown to interact with methylated histone H3K36 and is implicated in the spreading of the dosage-compensation complex from its initial binding sites, defining a process of spreading by activation complexes analogous to that defined for silencing complexes.
Abstract - | Full Text - The MSL3 chromodomain directs a key targeting step for dosage compensation of the Drosophila melanogaster X chromosome | PDF (1,348 KB) - The MSL3 chromodomain directs a key targeting step for dosage compensation of the Drosophila melanogaster X chromosome | Supplementary information
Cooperative three-step motions in catalytic subunits of F1-ATPase correlate with 80° and 40° substep rotations - pp1326 - 1333
Tomoko Masaike, Fumie Koyama-Horibe, Kazuhiro Oiwa, Masasuke Yoshida & Takayuki Nishizaka
doi:10.1038/nsmb.1510
F1 ATPase contains three catalytic subunits that hydrolyze ATP, causing the central 
subunit to rotate. Now, using fluorescent tags, conformational changes in and rotation of are observed simultaneously within the same complex, allowing the motions in to be correlated with catalytic events and ultimately rotation.
Abstract - | Full Text - Cooperative three-step motions in catalytic subunits of F1-ATPase correlate with 80° and 40° substep rotations | PDF (2,597 KB) - Cooperative three-step motions in catalytic subunits of F1-ATPase correlate with 80° and 40° substep rotations | Supplementary information
Molecular basis of Pirh2-mediated p53 ubiquitylation - pp1334 - 1342
Yi Sheng, Rob C Laister, Alexander Lemak, Bin Wu, Elizabeth Tai, Shili Duan, Jonathan Lukin, Maria Sunnerhagen, Sampath Srisailam, Murthy Karra, Sam Benchimol & Cheryl H Arrowsmith
doi:10.1038/nsmb.1521
Pirh2 is one of several ubiquitin ligases known to modify and negatively regulate p53. Solution studies reveal the structures of the three Pirh2 domains and indicate that the C-terminal domain of Pirh2 interacts with the p53 tetramerization domain. Additional data suggest that Pirh2 preferentially modifies the tetrameric, transcriptionally active form of p53 for proteasome-mediated degradation.
Abstract - | Full Text - Molecular basis of Pirh2-mediated p53 ubiquitylation | PDF (1,033 KB) - Molecular basis of Pirh2-mediated p53 ubiquitylation | Supplementary information
Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1 - pp1343 - 1351
Marianna Teplova & Dinshaw J Patel
doi:10.1038/nsmb.1519
Muscleblind-like (MBNL) proteins have been implicated in alternative-splicing regulation during development, and altered levels of these proteins have been implicated in myotonic dystrophy. The structure of the MBNL1 zinc finger domains in complex with RNA indicates how the target sequence is recognized and suggests that an antiparallel arrangement of the zinc fingers causes a trajectory reversal in the pre-mRNA target. The potential role of such generated looped segments in alternative splicing is discussed.
Abstract - | Full Text - Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1 | PDF (1,091 KB) - Structural insights into RNA recognition by the alternative-splicing regulator muscleblind-like MBNL1 | Supplementary information
