Table of contents
November 2008, Volume 15 No 11 pp1127-1231
About the coverEditorial
Enlightening biology - p1127
doi:10.1038/nsmb1108-1127
This year's Nobel Prize in Chemistry recognized the researchers whose work literally illuminated biological processes.
Full Text - Enlightening biology | PDF (218 KB) - Enlightening biology
News and Views
A major switch for the Fanconi anemia DNA damage–response pathway - pp1128 - 1130
Weidong Wang
doi:10.1038/nsmb1108-1128
The Fanconi anemia pathway is part of the DNA-damage network including breast cancer–susceptibility proteins BRCA1 and BRCA2. This pathway is activated by the ataxia telangiectasia and Rad3–related (ATR) kinase, but the underlying mechanism remains unclear. A new study demonstrates that a major switch activating the pathway is the ATR-dependent phosphorylation of FANCI.
Full Text - A major switch for the Fanconi anemia DNA damage–response pathway | PDF (927 KB) - A major switch for the Fanconi anemia DNA damage–response pathway
See also: Article by Ishiai et al.
Integration of an electric-metal sensory experience in the Slo1 BK channel - pp1130 - 1132
Frank T Horrigan & Toshinori Hoshi
doi:10.1038/nsmb1108-1130
The open gate of the BK-type K+ channel is stabilized when the voltage-sensor domains (VSDs) are activated by depolarization and the intracellular Mg2+ sensors are occupied. A systematic investigation reveals that each Mg2+ is bound by the transmembrane VSD and cytoplasmic ligand-sensing domain from two adjacent subunits, suggesting that relative positions of sensor and gate domains of BK channels may differ substantially from those suggested by homology models.
Full Text - Integration of an electric-metal sensory experience in the Slo1 BK channel | PDF (657 KB) - Integration of an electric-metal sensory experience in the Slo1 BK channel
See also: Article by Yang et al.
An INKlination for epigenetic control of senescence - pp1133 - 1134
Gordon Peters
doi:10.1038/nsmb1108-1133
Much has been written and said about the links between the Ink4a-Arf locus, cellular senescence and stem-cell maintenance. Standing modestly in the shadows of these superstars of tumor suppression, the closely linked Ink4b gene is now emerging as a significant player in these events, and its regulation by a histone demethylase could provide new insights into how this remarkable locus is controlled.
Full Text - An INKlination for epigenetic control of senescence | PDF (282 KB) - An INKlination for epigenetic control of senescence
See also: Article by He et al.
How to pick a protein and pull at it - pp1135 - 1136
Tomonao Inobe, Daniel A Kraut & Andreas Matouschek
doi:10.1038/nsmb1108-1135
In this issue of Nature Structural & Molecular Biology, work on the bacterial AAA+ machine ClpX provides insight into how the ATPase subunits exert a translocating force on their substrates.
Full Text - How to pick a protein and pull at it | PDF (129 KB) - How to pick a protein and pull at it
See also: Article by Martin et al.
Research Highlights
Research highlights - p1137
Angela K Eggleston, Joshua M Finkelstein, Maria Hodges & Sabbi Lall
doi:10.1038/nsmb1108-1137
Full Text - Research highlights | PDF (151 KB) - Research highlights
Articles
FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway - pp1138 - 1146
Masamichi Ishiai, Hiroyuki Kitao, Agata Smogorzewska, Junya Tomida, Aiko Kinomura, Emi Uchida, Alihossein Saberi, Eiji Kinoshita, Emiko Kinoshita-Kikuta, Tohru Koike, Satoshi Tashiro, Stephen J Elledge & Minoru Takata
doi:10.1038/nsmb.1504
The Fanconi anemia pathway is involved in the signaling of DNA damage. Several Fanconi anemia proteins have been identified, but how the pathway is actually activated was unclear. Now, work on chicken DT40 cells indicates that phosphorylation of FANCI at multiple sites triggers FANCD2 monoubiquitination and DNA-damage repair.
Abstract - | Full Text - FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway | PDF (812 KB) - FANCI phosphorylation functions as a molecular switch to turn on the Fanconi anemia pathway | Supplementary information
See also: News and Views by Wang
Pore loops of the AAA+ ClpX machine grip substrates to drive translocation and unfolding - pp1147 - 1151
Andreas Martin, Tania A Baker & Robert T Sauer
doi:10.1038/nsmb.1503
The bacterial AAA+ ClpX unfolds substrates using the energy from ATP hydrolysis and delivers them to the associated protease ClpP. A loop with an aromatic-hydrophobic motif protrudes into the central pore of the ClpX hexamer and was known to be important for activity. Now mutational analysis using covalently linked subunits provides evidence that this loop actually grips the substrate and undergoes conformational changes to drive its translocation and unfolding.
Abstract - | Full Text - Pore loops of the AAA+ ClpX machine grip substrates to drive translocation and unfolding | PDF (1,374 KB) - Pore loops of the AAA+ ClpX machine grip substrates to drive translocation and unfolding
See also: News and Views by Inobe et al.
Activation of Slo1 BK channels by Mg2+ coordinated between the voltage sensor and RCK1 domains - pp1152 - 1159
Huanghe Yang, Jingyi Shi, Guohui Zhang, Junqiu Yang, Kelli Delaloye & Jianmin Cui
doi:10.1038/nsmb.1507
The voltage-sensor and RCK1 domains of BK channels act synergistically to sense electric and chemical signals. New data now indicate that the Mg2+-mediated interactions between these domains occurs between channel subunits, suggesting a structural arrangement that differs from other potassium channels.
Abstract - | Full Text - Activation of Slo1 BK channels by Mg2+ coordinated between the voltage sensor and RCK1 domains | PDF (960 KB) - Activation of Slo1 BK channels by Mg2+ coordinated between the voltage sensor and RCK1 domains | Supplementary information
See also: News and Views by Horrigan & Hoshi
The Janus-faced nature of the C2B domain is fundamental for synaptotagmin-1 function - pp1160 - 1168
Mingshan Xue, Cong Ma, Timothy K Craig, Christian Rosenmund & Josep Rizo
doi:10.1038/nsmb.1508
The Ca2+ binding loops of the C2A and C2B domains of synaptotagmin-1 are known to be important in Ca2+-triggered neurotransmitter release. Biophysical and in vivo data now indicate that a basic patch on the opposite face of the C2B domain has an equally crucial but Ca2+-independent role.
Abstract - | Full Text - The Janus-faced nature of the C2B domain is fundamental for synaptotagmin-1 function | PDF (895 KB) - The Janus-faced nature of the C2B domain is fundamental for synaptotagmin-1 function | Supplementary information
The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15Ink4b - pp1169 - 1175
Jin He, Eric M Kallin, Yu-ichi Tsukada & Yi Zhang
doi:10.1038/nsmb.1499
The Ink4a-Arf-Ink4b locus has a role in both senescence and tumorigenesis, and dysregulation can result in tumorigenesis. The Jhdm1b Jumonji family protein is now shown to be an H3K36 demethylase and is implicated in regulating cellular proliferation and senescence through p15Ink4b.
Abstract - | Full Text - The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15Ink4b | PDF (569 KB) - The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15Ink4b | Supplementary information
See also: News and Views by Peters
De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes - pp1176 - 1183
Silvina Epsztejn-Litman, Nirit Feldman, Monther Abu-Remaileh, Yoel Shufaro, Ariela Gerson, Jun Ueda, Rachel Deplus, François Fuks, Yoichi Shinkai, Howard Cedar & Yehudit Bergman
doi:10.1038/nsmb.1476
G9a is involved in gene silencing during early embryonic development, catalyzing the methylation of H3K9, which results in heterochromatinization, and also promoting methylation of DNA de novo. These two G9a activities are now dissected, and de novo DNA methylation is shown to occur via recruitment of Dnmt3a/3b and to be necessary and sufficient to prevent reprogramming.
Abstract - | Full Text - De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes | PDF (725 KB) - De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes | Supplementary information
Phosphorylation of APOBEC3G by protein kinase A regulates its interaction with HIV-1 Vif - pp1184 - 1191
Kotaro Shirakawa, Akifumi Takaori-Kondo, Masaru Yokoyama, Taisuke Izumi, Masashi Matsui, Katsuhiro Io, Toshihiro Sato, Hironori Sato & Takashi Uchiyama
doi:10.1038/nsmb.1497
The antiretroviral cytidine deaminase APOBEC3G inhibits HIV-1 replication, but the enzyme is targeted for degradation by HIV-1 Vif. Protein kinase A activity is known to be elevated in HIV-1–infected T cells. New data indicate that phosphorylation of APOBEC3G by protein kinase A renders the protein less susceptible to Vif-mediated degradation.
Abstract - | Full Text - Phosphorylation of APOBEC3G by protein kinase A regulates its interaction with HIV-1 Vif | PDF (696 KB) - Phosphorylation of APOBEC3G by protein kinase A regulates its interaction with HIV-1 Vif | Supplementary information
A quantitative model of transcription factor–activated gene expression - pp1192 - 1198
Harold D Kim & Erin K O'Shea
doi:10.1038/nsmb.1500
The effect of transcription factor affinity and accessibility on gene expression has been difficult to quantify and model. The contribution of both transcription factor binding affinity and nucleosomes to tuning and diversification of gene expression output is now quantitatively uncovered, and a model that can be applied to other eukaryotic gene expression systems generated.
Abstract - | Full Text - A quantitative model of transcription factor–activated gene expression | PDF (624 KB) - A quantitative model of transcription factor–activated gene expression | Supplementary information
Structural elucidation of a PRP8 core domain from the heart of the spliceosome - pp1199 - 1205
Dustin B Ritchie, Matthew J Schellenberg, Emily M Gesner, Sheetal A Raithatha, David T Stuart & Andrew M MacMillan
doi:10.1038/nsmb.1505
PDB code
3D view
The spliceosome consists of five RNAs and more than 100 associated proteins. One of these, PRP8, is both one of the largest and most highly conserved spliceosomal proteins. Previous genetic and cross-linking data pointed to the importance of domain IV of PRP8 in spliceosome assembly and/or catalysis. Its structure has now been solved and found to contain an RNase H fold, suggestive of an RNA binding surface. The RNA binding data suggest that the PRP8 core recognizes, rather than a specific sequence, a structure resembling the four-helix junction proposed for the catalytically active U2/U6 snRNA interaction.
Abstract - | Full Text - Structural elucidation of a PRP8 core domain from the heart of the spliceosome | PDF (1,131 KB) - Structural elucidation of a PRP8 core domain from the heart of the spliceosome | Supplementary information
Localization of Prp8, Brr2, Snu114 and U4/U6 proteins in the yeast tri-snRNP by electron microscopy - pp1206 - 1212
Irina Häcker, Bjoern Sander, Monika M Golas, Elmar Wolf, Elif Karagöz, Berthold Kastner, Holger Stark, Patrizia Fabrizio & Reinhard Lührmann
doi:10.1038/nsmb.1506
The tri-snRNP is the largest preassembled unit of the spliceosome, and its components are key to the splicing reaction. The overall structure and conformations of the yeast tri-snRNP are now analyzed by EM, and the general positions of some of its major protein components mapped.
Abstract - | Full Text - Localization of Prp8, Brr2, Snu114 and U4/U6 proteins in the yeast tri-snRNP by electron microscopy | PDF (840 KB) - Localization of Prp8, Brr2, Snu114 and U4/U6 proteins in the yeast tri-snRNP by electron microscopy | Supplementary information
Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5 - pp1213 - 1220
Weijun Chen, Suvana S Lam, Hema Srinath, Zhaozhao Jiang, John J Correia, Celia A Schiffer, Katherine A Fitzgerald, Kai Lin & William E Royer Jr
doi:10.1038/nsmb.1496
PDB code
3D view
The interferon regulatory factors (IRFs) are involved in the innate immune response and are activated by phosphorylation. The structure of a pseudophosphorylated IRF5 activation domain now reveals structural changes in the activated form that would turn an autoinhibitory region into a dimerization interface. In vivo analysis supports the relevance of such a dimer to transcriptional activation.
Abstract - | Full Text - Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5 | PDF (1,221 KB) - Insights into interferon regulatory factor activation from the crystal structure of dimeric IRF5 | Supplementary information
Brief Communication
Structural basis for exon recognition by a group II intron - pp1221 - 1222
Navtej Toor, Kanagalaghatta Rajashankar, Kevin S Keating & Anna Marie Pyle
doi:10.1038/nsmb.1509
Group II introns are retroelements that have invaded the genomes of many prokaryotes and eukaryotes. The structure of a self-spliced group IIC intron cocrystallized with ligated exons (the target substrate) reveals the metal ions that have a role in catalysis and the intron sequences that are important in exon recognition in group II introns.
Abstract - | Full Text - Structural basis for exon recognition by a group II intron | PDF (393 KB) - Structural basis for exon recognition by a group II intron | Supplementary information
Analysis
The 'glutamate switch' provides a link between ATPase activity and ligand binding in AAA+ proteins - pp1223 - 1227
Xiaodong Zhang & Dale B Wigley
doi:10.1038/nsmb.1501
The ATPase activity of AAA+ proteins is regulated by their interaction with ligands, but depending on the particular protein it can be stimulated or inhibited, and the mechanism for such control remained unclear. An analysis of previous structural data on various AAA+ proteins now reveals that a conserved glutamate residue adopts two conformations and and thus regulates the ATPase activity.
Abstract - | Full Text - The 'glutamate switch' provides a link between ATPase activity and ligand binding in AAA+ proteins | PDF (622 KB) - The 'glutamate switch' provides a link between ATPase activity and ligand binding in AAA+ proteins
An equivalent metal ion in one- and two-metal-ion catalysis - pp1228 - 1231
Wei Yang
doi:10.1038/nsmb.1502
Most known nucleotidyl-transfer enzymes use two metal ions for catalysis, but some enzymes use only one divalent cation in their active sites. A comparative analysis of previously available structural data reveals that the one-metal-ion enzymes use a similar mechanism to coordinate their single metal ion, which corresponds, functionally and structurally, to metal ion B in the two-metal-ion enzymes.
Abstract - | Full Text - An equivalent metal ion in one- and two-metal-ion catalysis | PDF (480 KB) - An equivalent metal ion in one- and two-metal-ion catalysis
