Focus on Protein Folding

Folding to function - p573

doi:10.1038/nsmb0609-573

The practice of origami dates from the 1600s, but this cannot compare to how long proteins have been evolving form and function. How proteins achieve their correct shape is the subject of this special Focus.

Full Text - Folding to function | PDF (215 KB) - Folding to function

Focus on Protein Folding

Converging concepts of protein folding in vitro and in vivo - pp574 - 581

F Ulrich Hartl & Manajit Hayer-Hartl

doi:10.1038/nsmb.1591

Abstract - | Full Text - Converging concepts of protein folding in vitro and in vivo | PDF (1,518 KB) - Converging concepts of protein folding in vitro and in vivo

Focus on Protein Folding

An expanding arsenal of experimental methods yields an explosion of insights into protein folding mechanisms - pp582 - 588

Alice I Bartlett & Sheena E Radford

doi:10.1038/nsmb.1592

Abstract - | Full Text - An expanding arsenal of experimental methods yields an explosion of insights into protein folding mechanisms | PDF (558 KB) - An expanding arsenal of experimental methods yields an explosion of insights into protein folding mechanisms

Focus on Protein Folding

The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins - pp589 - 597

Günter Kramer, Daniel Boehringer, Nenad Ban & Bernd Bukau

doi:10.1038/nsmb.1614

Abstract - | Full Text - The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins | PDF (822 KB) - The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins

Focus on Protein Folding

Unraveling infectious structures, strain variants and species barriers for the yeast prion [PSI⁺] - pp598 - 605

Peter M Tessier & Susan Lindquist

doi:10.1038/nsmb.1617

Abstract - | Full Text - Unraveling infectious structures, strain variants and species barriers for the yeast prion [PSI+] | PDF (1,403 KB) - Unraveling infectious structures, strain variants and species barriers for the yeast prion [PSI+]

Focus on Protein Folding

Cellular mechanisms of membrane protein folding - pp606 - 612

William R Skach

doi:10.1038/nsmb.1600

Abstract - | Full Text - Cellular mechanisms of membrane protein folding | PDF (1,025 KB) - Cellular mechanisms of membrane protein folding

A new way to initiate mRNA degradation - pp613 - 614

William Marzluff

doi:10.1038/nsmb0609-613

Removal of the poly(A) tail is the initial step in targeting an mRNA for degradation in budding yeast as well as in metazoans. But in fission yeast a new study reveals an additional pathway that adds uridines to the poly(A) tail of mRNA to initiate the degradation pathway.

Full Text - A new way to initiate mRNA degradation | PDF (181 KB) - A new way to initiate mRNA degradation

See also: Article by Rissland & Norbury

Activating apoptosis - p614

Sabbi Lall

doi:10.1038/nsmb0609-614

Full Text - Activating apoptosis | PDF (152 KB) - Activating apoptosis

Research highlights - p615

doi:10.1038/nsmb0609-615

Full Text - Research highlights | PDF (231 KB) - Research highlights

Decapping is preceded by 3' uridylation in a novel pathway of bulk mRNA turnover - pp616 - 623

Olivia S Rissland & Chris J Norbury

doi:10.1038/nsmb.1601

Turnover of mRNA has mainly been studied in the budding yeast, Saccharomyces cerevisiae, and is thought to be initiated by deadenylation. Now Rissland and Norbury reveal that additional, parallel decay pathways are at work in the fission yeast, Schizosaccharomyces pombe. They find that mRNA decapping is frequently independent of deadenylation and that Cid1-dependent uridylation of polyadenylated mRNAs seems to stimulate decapping as part of a novel mRNA turnover pathway. As human cells contain Cid1 orthologs, uridylation may form the basis of a widespread, conserved mechanism of mRNA decay.

Abstract - | Full Text - Decapping is preceded by 3' uridylation in a novel pathway of bulk mRNA turnover | PDF (606 KB) - Decapping is preceded by 3' uridylation in a novel pathway of bulk mRNA turnover | Supplementary information

See also: News and Views by Marzluff

PKC maturation is promoted by nucleotide pocket occupation independently of intrinsic kinase activity - pp624 - 630

Angus J M Cameron, Cristina Escribano, Adrian T Saurin, Brenda Kostelecky & Peter J Parker

doi:10.1038/nsmb.1606

Protein kinase C epsilon (PKC) priming involves phosphorylation of the kinase domain at 3 different sites. Whether these phosphorylation events were autocatalytic was unclear. Now Parker and colleagues use different PKC mutants and inhibitors to demonstrate that the occupancy of the nucleotide binding pocket, and not catalytic activity, promote priming of PKC.

Abstract - | Full Text - PKC maturation is promoted by nucleotide pocket occupation independently of intrinsic kinase activity | PDF (562 KB) - PKC maturation is promoted by nucleotide pocket occupation independently of intrinsic kinase activity | Supplementary information

The N-terminal domain of GluR6-subtype glutamate receptor ion channels - pp631 - 638

Janesh Kumar, Peter Schuck, Rongsheng Jin & Mark L Mayer

doi:10.1038/nsmb.1613

• PDB code

  • 3H6G
  • 3H6H

• 3D view

  • 3H6G
  • 3H6H

The amino-terminal domain (ATD) of ionotropic glutamate receptors (iGluRs) mediates their assembly into AMPA-, kainate- and NMDA-sensitive subtypes. The crystal structure of the ATD from the kainate receptor GluR6 reveals a dimeric organization and likely determinants for subtype-selective assembly.

Abstract - | Full Text - The N-terminal domain of GluR6-subtype glutamate receptor ion channels | PDF (1,241 KB) - The N-terminal domain of GluR6-subtype glutamate receptor ion channels | Supplementary information

Loss of the Mili-interacting Tudor domain–containing protein-1 activates transposons and alters the Mili-associated small RNA profile - pp639 - 646

Michael Reuter, Shinichiro Chuma, Takashi Tanaka, Thomas Franz, Alexander Stark & Ramesh S Pillai

doi:10.1038/nsmb.1615

piRNAs have been implicated in transposon silencing. Tudor domain–containing protein-1 (Tdrd1) is now shown to interact with the mouse Piwi ortholog Mili and be part of a complex that contains Mili-associated piRNAs. Interaction occurs through the N terminus of Mili, which is dimethylated, a modification that promotes Tdrd1 interaction. The Tdrd1 mutant shares phenotypes with the Mili mutant but shows a strong effect on the nature of the small RNA pool associated with Mili.

Abstract - | Full Text - Loss of the Mili-interacting Tudor domain–containing protein-1 activates transposons and alters the Mili-associated small RNA profile | PDF (775 KB) - Loss of the Mili-interacting Tudor domain–containing protein-1 activates transposons and alters the Mili-associated small RNA profile | Supplementary information

Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes - pp647 - 651

Frank Striebel, Frank Imkamp, Markus Sutter, Martina Steiner, Azad Mamedov & Eilika Weber-Ban

doi:10.1038/nsmb.1597

Pupylation is the bacterial equivalent of ubiquitin conjugation, and it involves C-terminal Pup conjugation to lysines to target proteins for proteasomal degradation. This modification reaction has now been reconstituted in vitro using enzymes from the pathogen Mycobacterium tuberculosis. The Pup deamidase (Dop) of this pathway has been defined, and PafA has been shown to conjugate deamidated Pup to substrates.

Abstract - | Full Text - Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes | PDF (409 KB) - Bacterial ubiquitin-like modifier Pup is deamidated and conjugated to substrates by distinct but homologous enzymes | Supplementary information

Antidepressant specificity of serotonin transporter suggested by three LeuT–SSRI structures - pp652 - 657

Zheng Zhou, Juan Zhen, Nathan K Karpowich, Christopher J Law, Maarten E A Reith & Da-Neng Wang

doi:10.1038/nsmb.1602

• PDB code

  • 3GWU
  • 3GWV
  • 3GWW

• 3D view

  • 3GWU
  • 3GWV
  • 3GWW

Sertraline (Zoloft) and fluoxetine (Prozac) are selective serotonin-reuptake inhibitors (SSRIs) that are widely prescribed to treat depression. They bind to the presynaptic plasma membrane serotonin transporter (SERT) and inhibit serotonin uptake. Both these drugs possess halogen atoms, but the structural basis for the specificity of SERT for these inhibitors was not known. Zhou et al. now report the crystal structure of LeuT, a bacterial SERT homolog in complex with three different SSRIs. The halogen atoms of all three bind within exactly the same pocket of LeuT, and mutations within this pocket in SERT markedly reduce the transporter's affinity for SSRIs but not for tricyclic antidepressants.

Abstract - | Full Text - Antidepressant specificity of serotonin transporter suggested by three LeuT–SSRI structures | PDF (589 KB) - Antidepressant specificity of serotonin transporter suggested by three LeuT–SSRI structures | Supplementary information

E2 interaction and dimerization in the crystal structure of TRAF6 - pp658 - 666

Qian Yin, Su-Chang Lin, Betty Lamothe, Miao Lu, Yu-Chih Lo, Gregory Hura, Lixin Zheng, Rebecca L Rich, Alejandro D Campos, David G Myszka, Michael J Lenardo, Bryant G Darnay & Hao Wu

doi:10.1038/nsmb.1605

• PDB code

  • 3HCS
  • 3HCT
  • 3HCU

• 3D view

  • 3HCS
  • 3HCT
  • 3HCU

The signaling adaptor TRAF6 is a ubiquitin E3 ligase whose activity can lead to activation of NF-B and MAPK pathways. New data based on the structure of TRAF6 in complex with the ubiquitin E2 Ubc13 suggest that other TRAFs do not interact with Ubc13 and that oligomerization of TRAF6 is needed for downstream signal transduction.

Abstract - | Full Text - E2 interaction and dimerization in the crystal structure of TRAF6 | PDF (1,006 KB) - E2 interaction and dimerization in the crystal structure of TRAF6 | Supplementary information

Structural insight into the quinolone–DNA cleavage complex of type IIA topoisomerases - pp667 - 669

Ivan Laponogov, Maninder K Sohi, Dennis A Veselkov, Xiao-Su Pan, Ritica Sawhney, Andrew W Thompson, Katherine E McAuley, L Mark Fisher & Mark R Sanderson

doi:10.1038/nsmb.1604

• PDB code

  • 3FOE
  • 3FOF

• 3D view

  • 3FOE
  • 3FOF

Topoisomerases alter DNA topology, an essential activity in all organisms. Bacterial type II topoisomerases are targets for antimicrobials such as quinolones, whose binding mode was unclear. Now the crystal structures of pneumococcal topoisomerase IV in a DNA cleavage complex bound to moxifloxacin or clinafloxacin provide insight into how these drugs work and how bacteria can acquire resistance.

Abstract - | Full Text - Structural insight into the quinolone–DNA cleavage complex of type IIA topoisomerases | PDF (669 KB) - Structural insight into the quinolone–DNA cleavage complex of type IIA topoisomerases | Supplementary information

Cancer-associated regulation of alternative splicing - pp670 - 676

Julian P Venables, Roscoe Klinck, ChuShin Koh, Julien Gervais-Bird, Anne Bramard, Lyna Inkel, Mathieu Durand, Sonia Couture, Ulrike Froehlich, Elvy Lapointe, Jean-François Lucier, Philippe Thibault, Claudine Rancourt, Karine Tremblay, Panagiotis Prinos, Benoit Chabot & Sherif Abou Elela

doi:10.1038/nsmb.1608

A large-scale screen for changes in alternative splice forms in cancer now reveals that almost half of the active alternative splicing events are shifted in breast and ovarian cancer tissues. In addition, many of these changes occur near consensus binding sequences for FOX2 binding sites. This correlates with changes in Fox2 expression or splicing in tissues assessed, and FOX2 depletion results in similar shifts in splice isoforms.

Abstract - | Full Text - Cancer-associated regulation of alternative splicing | PDF (1,530 KB) - Cancer-associated regulation of alternative splicing | Supplementary information