Table of contents
March 2009, Volume 16 No 3 pp229-344
About the coverEditorial
Stimulating science - p229
doi:10.1038/nsmb0309-229
The economic benefits of biomedical research are recognized by governments around the world, but investment in science should go beyond profitability.
Full Text - Stimulating science | PDF (249 KB) - Stimulating science
Obituary
Frederic M Richards 1925–2009 - pp230 - 232
Wendell A Lim
doi:10.1038/nsmb0309-230
Full Text - Frederic M Richards 1925–2009 | PDF (765 KB) - Frederic M Richards 1925–2009
News and Views
Universal epitopes of influenza virus hemagglutinins? - pp233 - 234
Taia T Wang & Peter Palese
doi:10.1038/nsmb.1574
The influenza virus has proved an elusive target in the development of broadly protective vaccines. A new study identifies an antibody with broad neutralizing activity against influenza viruses of different subtypes. The antibody recognizes a highly conserved region on the viral hemagglutinin that may be targeted to prevent infection.
Full Text - Universal epitopes of influenza virus hemagglutinins? | PDF (1,455 KB) - Universal epitopes of influenza virus hemagglutinins?
See also: Article by Sui et al.
Visualizing the twists and turns of a molecular chaperone - pp235 - 236
Len Neckers, Shinji Tsutsumi & Mehdi Mollapour
doi:10.1038/nsmb0309-235
Intermediate conformations of the Hsp90 ATPase cycle have been identified in solution by fluorescence resonance energy transfer, and the impact of nucleotides and of modulatory cochaperones has been visualized in real time.
Full Text - Visualizing the twists and turns of a molecular chaperone | PDF (733 KB) - Visualizing the twists and turns of a molecular chaperone
See also: Article by Mickler et al. | Article by Hessling et al.
Research Highlights
Research highlights - p237
doi:10.1038/nsmb0309-237
Full Text - Research highlights | PDF (178 KB) - Research highlights
Articles
Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding - pp238 - 246
Irene Díaz-Moreno, David Hollingworth, Thomas A Frenkiel, Geoff Kelly, Stephen Martin, Steven Howell, MaríaFlor García-Mayoral, Roberto Gherzi, Paola Briata & Andres Ramos
doi:10.1038/nsmb.1558
PDB code
3D view
KSRP is involved in mRNA instability, a role that is repressed upon AKT kinase–mediated phosphorylation, which promotes 14-3-3 interaction. This modification site is now shown to be exposed upon AKT phosphorylation through unfolding of the KH1 domain of KSRP, an event that allows 14-3-3 interaction, which in turn affects nuclear cytoplasmic partitioning.
Abstract - | Full Text - Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding | PDF (1,027 KB) - Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding | Supplementary information
The mRNA export protein DBP5 binds RNA and the cytoplasmic nucleoporin NUP214 in a mutually exclusive manner - pp247 - 254
Holger von Moeller, Claire Basquin & Elena Conti
doi:10.1038/nsmb.1561
The DEAD-box protein DBP5 is involved in yeast mRNA export, though the mechanism by which it helps to remodel and release transcripts on the cytoplasmic face of the nuclear pore complex has been unclear. The structures of DBP5 in complex with the mRNA and AMPPNP, as well as with the nucleoporin NUP214, indicate that the transcript and nucleoporin compete for the same binding site, suggesting a model for the sequence of events occurring at the last step of export.
Abstract - | Full Text - The mRNA export protein DBP5 binds RNA and the cytoplasmic nucleoporin NUP214 in a mutually exclusive manner | PDF (791 KB) - The mRNA export protein DBP5 binds RNA and the cytoplasmic nucleoporin NUP214 in a mutually exclusive manner | Supplementary information
A complex gene regulatory mechanism that operates at the nexus of multiple RNA processing decisions - pp255 - 264
David S McPheeters, Nicole Cremona, Sham Sunder, Huei-Mei Chen, Nicole Averbeck, Janet Leatherwood & Jo Ann Wise
doi:10.1038/nsmb.1556
Meiosis is a highly conserved and tightly regulated process in which one round of DNA synthesis is followed by two rounds of division. By studying the expression of crs1 pre-mRNA, a meiotic cyclin in fission yeast, Wise and co-workers found that increased RNA accumulation during meiosis is not due to an increase in transcription but rather is a result of RNA processing and turnover. Moreover, they found that polyadenylation of crs1 is linked to splicing, a coupling previously thought to occur only in mammals. They suggest that this highly integrated crs1 regulatory system may allow a rapid response to adverse conditions.
Abstract - | Full Text - A complex gene regulatory mechanism that operates at the nexus of multiple RNA processing decisions | PDF (920 KB) - A complex gene regulatory mechanism that operates at the nexus of multiple RNA processing decisions | Supplementary information
Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses - pp265 - 273
Jianhua Sui, William C Hwang, Sandra Perez, Ge Wei, Daniel Aird, Li-mei Chen, Eugenio Santelli, Boguslaw Stec, Greg Cadwell, Maryam Ali, Hongquan Wan, Akikazu Murakami, Anuradha Yammanuru, Thomas Han, Nancy J Cox, Laurie A Bankston, Ruben O Donis, Robert C Liddington & Wayne A Marasco
doi:10.1038/nsmb.1566
PDB code
3D view
A group of neutralizing monoclonal antibodies (mAbs) targeting the influenza A hemagglutinin has been selected and characterized. Remarkably, these mAbs were able to neutralize a broad array of group 1 strains and could protect mice from infection when given prophylactically or therapeutically. The crystal structure of one such mAb in complex with hemagglutinin provides insight into its mechanism of neutralization and broad specificity.
Abstract - | Full Text - Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses | PDF (1,111 KB) - Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses | Supplementary information
See also: News and Views by Wang & Palese
Transient ribosomal attenuation coordinates protein synthesis and co-translational folding - pp274 - 280
Gong Zhang, Magdalena Hubalewska & Zoya Ignatova
doi:10.1038/nsmb.1554
Rare codons along transcripts have been proposed to influence the local rate of translation and the folding of nascent polypeptide chains. Now this idea is demonstrated for a bacterial protein: rare-codon clusters are shown to affect translation rates, and this was important for efficient protein folding in vitro and in vivo.
Abstract - | Full Text - Transient ribosomal attenuation coordinates protein synthesis and co-translational folding | PDF (680 KB) - Transient ribosomal attenuation coordinates protein synthesis and co-translational folding | Supplementary information
The large conformational changes of Hsp90 are only weakly coupled to ATP hydrolysis - pp281 - 286
Moritz Mickler, Martin Hessling, Christoph Ratzke, Johannes Buchner & Thorsten Hugel
doi:10.1038/nsmb.1557
The Hsp90 chaperone is responsible for the stabilization of a large variety of regulatory proteins. Single-molecule FRET was used to examine the conformational dynamics of Hsp90 in its different nucleotide-bound states. The findings suggest that, in the absence of substrate and cochaperone proteins, Hsp90's conformational changes are not strongly coupled to ATP hydrolysis.
Abstract - | Full Text - The large conformational changes of Hsp90 are only weakly coupled to ATP hydrolysis | PDF (806 KB) - The large conformational changes of Hsp90 are only weakly coupled to ATP hydrolysis | Supplementary information
See also: News and Views by Neckers et al.
Dissection of the ATP-induced conformational cycle of the molecular chaperone Hsp90 - pp287 - 293
Martin Hessling, Klaus Richter & Johannes Buchner
doi:10.1038/nsmb.1565
The Hsp90 chaperone is responsible for the stabilization of a large variety of regulatory proteins. By labeling the subunits in the Hsp90 homodimer with different dyes and in different positions, the kinetics of Hsp90 conformational changes along the ATPase cycle was characterized, revealing different intermediate states and the different roles of cochaperones.
Abstract - | Full Text - Dissection of the ATP-induced conformational cycle of the molecular chaperone Hsp90 | PDF (715 KB) - Dissection of the ATP-induced conformational cycle of the molecular chaperone Hsp90 | Supplementary information
See also: News and Views by Neckers et al.
A Mek1–Mek2 heterodimer determines the strength and duration of the Erk signal - pp294 - 303
Federica Catalanotti, Gloria Reyes, Veronika Jesenberger, Gergana Galabova-Kovacs, Ricardo de Matos Simoes, Oliviero Carugo & Manuela Baccarini
doi:10.1038/nsmb.1564
Mek1 and Mek2 are kinases that phosphorylate Erk, participating in the signal transduction pathway controlling cellular growth and adhesion. Though closely related, there are clear functional differences, with Mek1 being subject to negative-feedback regulation via phosphorylation by Erk. Now Mek1 and Mek2 are shown to form a heterodimer in vivo, in which Mek2 activity is also controlled by Erk phosphorylation of Mek1.
Abstract - | Full Text - A Mek1–Mek2 heterodimer determines the strength and duration of the Erk signal | PDF (906 KB) - A Mek1–Mek2 heterodimer determines the strength and duration of the Erk signal | Supplementary information
PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing - pp304 - 311
Quan Zhao, Gerhard Rank, Yuen T Tan, Haitao Li, Robert L Moritz, Richard J Simpson, Loretta Cerruti, David J Curtis, Dinshaw J Patel, C David Allis, John M Cunningham & Stephen M Jane
doi:10.1038/nsmb.1568
Mammalian gene silencing is associated with both histone and DNA methylation. The PRMT5 arginine histone methyltransferase is now found to affect DNA methylation at the 
-globin locus in mice. This is mediated by an effect on recruitment of the DNA methyltransferase DNMT3A, but through interaction with the product of PRMT5 activity. This suggests that DNMT3A reads the histone methylation, coupling it to nearby DNA methylation.
Abstract - | Full Text - PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing | PDF (598 KB) - PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing | Supplementary information
Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294 - pp312 - 317
Yanqi Chang, Xing Zhang, John R Horton, Anup K Upadhyay, Astrid Spannhoff, Jin Liu, James P Snyder, Mark T Bedford & Xiaodong Cheng
doi:10.1038/nsmb.1560
PDB code
3D view
The G9a-like lysine methyltransferases can be inhibited by the small molecule BIX-01294, recently identified through a chemical screen and shown to be capable of replacing Oct3/4. The structure of GLP in complex with BIX-01294 indicates an overlap with the known position of histone peptide binding, and further work indicates that the drug inhibits methylation of DNMT1, indicating that it is enzyme specific but non specific with regard to substrate.
Abstract - | Full Text - Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294 | PDF (731 KB) - Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294 | Supplementary information
The mechanism of folding of Im7 reveals competition between functional and kinetic evolutionary constraints - pp318 - 324
Claire T Friel, D Alastair Smith, Michele Vendruscolo, Joerg Gsponer & Sheena E Radford
doi:10.1038/nsmb.1562
Im7 is a small Escherichia coli colicin binding protein that uses a remarkably complex folding pathway. Analysis of the Im7 folding landscape reveals details of the earliest transition state in its folding pathway and indicates that the formation of non-native contacts that result in intermediate folding states is necessary to maintain elements essential to the protein's function.
Abstract - | Full Text - The mechanism of folding of Im7 reveals competition between functional and kinetic evolutionary constraints | PDF (845 KB) - The mechanism of folding of Im7 reveals competition between functional and kinetic evolutionary constraints | Supplementary information
Helix sliding in the stalk coiled coil of dynein couples ATPase and microtubule binding - pp325 - 333
Takahide Kon, Kenji Imamula, Anthony J Roberts, Reiko Ohkura, Peter J Knight, I R Gibbons, Stan A Burgess & Kazuo Sutoh
doi:10.1038/nsmb.1555
The ATPase and the microtubule binding domains of dynein are separated by a long stalk coiled coil, which has to communicate and coordinate the activities of these domains along the mechanochemical cycle. Now this communication is shown to occur via sliding of the 
-helices of the coiled coil.
Abstract - | Full Text - Helix sliding in the stalk coiled coil of dynein couples ATPase and microtubule binding | PDF (913 KB) - Helix sliding in the stalk coiled coil of dynein couples ATPase and microtubule binding | Supplementary information
Cyanobacterial photosystem II at 2.9-Å resolution and the role of quinones, lipids, channels and chloride - pp334 - 342
Albert Guskov, Jan Kern, Azat Gabdulkhakov, Matthias Broser, Athina Zouni & Wolfram Saenger
doi:10.1038/nsmb.1559
Photosystem II (PSII) catalyzes the first light-dependent step in photosynthesis. An improved structural model of a cyanobacterial PSII provides complete assignment of all subunits in the complex and reveals possible channels used for the transport of protons, oxygen and water to the thylakoid lumen.
Abstract - | Full Text - Cyanobacterial photosystem II at 2.9-Å resolution and the role of quinones, lipids, channels and chloride | PDF (1,321 KB) - Cyanobacterial photosystem II at 2.9-Å resolution and the role of quinones, lipids, channels and chloride | Supplementary information
Brief Communication
Cocrystal structure of a class I preQ1 riboswitch reveals a pseudoknot recognizing an essential hypermodified nucleobase - pp343 - 344
Daniel J Klein, Thomas E Edwards & Adrian R Ferré-D'Amaré
doi:10.1038/nsmb.1563
Riboswitches are RNA domains that alter gene expression in response to ligand binding. The structure of the Bacillus subtilis preQ1 ribsoswitch, which recognizes the conserved modified nucleobase preQ1, in complex with its ligand indicates how an RNA of only 34 nucleotides recognizes its ligand.
Abstract - | Full Text - Cocrystal structure of a class I preQ1 riboswitch reveals a pseudoknot recognizing an essential hypermodified nucleobase | PDF (406 KB) - Cocrystal structure of a class I preQ1 riboswitch reveals a pseudoknot recognizing an essential hypermodified nucleobase | Supplementary information
