TABLE OF CONTENTS
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May 2014 Volume 21, Issue 5 |
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News and Views
Articles
Brief Communication
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Nature Structural & Molecular Biology FOCUS ON UBIQUITIN
Ubiquitin and ubiquitin-like proteins have central roles in regulating cellular processes and homeostasis. This Focus examines our understanding of the ubiquitination reaction and the mechanisms by which ubiquitin and related modifications affect key cellular functions.
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Obituary | Top |
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Iain D Campbell 1941-2014 pp427 - 428 Christina Redfield doi:10.1038/nsmb.2821
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News and Views | Top |
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Articles | Top |
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Crystal structure of ATP-bound Get3–Get4–Get5 complex reveals regulation of Get3 by Get4 pp437 - 442 Harry B Gristick, Meera Rao, Justin W Chartron, Michael E Rome, Shu-ou Shan et al. doi:10.1038/nsmb.2813 Tail-anchor proteins are targeted post-translationally to the endoplasmic reticulum via the conserved GET pathway, in which the Get4–Get5 complex mediates delivery of substrates to Get3, the central targeting factor. The crystal structure of the ATP-bound Get3–Get4–Get5 complex and functional analyses reveal how Get4–Get5 primes Get3 for substrate loading.
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Structural basis of recognition of interferon-a receptor by tyrosine kinase 2 pp443 - 448 Heidi J A Wallweber, Christine Tam, Yvonne Franke, Melissa A Starovasnik and Patrick J Lupardus doi:10.1038/nsmb.2807 How the four JAK kinases discriminate between different cytokine receptors is not well understood. The first crystal structure of a JAK kinase (TYK2) bound to a cytokine receptor (INFAR1) now exposes a multipoint interaction mode that involves an atypical phosphoindependent interaction between TYK2's SH2 domain and INFAR1's conserved box2 motif.
See also: News and Views by McNally & Eck
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Kin28 regulates the transient association of Mediator with core promoters pp449 - 455 Célia Jeronimo and François Robert doi:10.1038/nsmb.2810 The genomic localization of Mediator in budding yeast is now assessed, revealing that Mediator remains associated with upstream activating sequences until it becomes transiently associated with core promoters during initiation. Phosphorylation of the CTD of Rpb1 at Ser5 by Kin28 releases Mediator prior to elongation.
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Conformational changes required for H+/Cl− exchange mediated by a CLC transporter pp456 - 463 Daniel Basilio, Kristin Noack, Alessandra Picollo and Alessio Accardi doi:10.1038/nsmb.2814 CLC-type H+/Cl− exchangers are known to be regulated by voltage and H+ and Cl−concentrations, but their gating mechanism remains poorly understood. New data now suggest that transport by the CLCs is regulated by two gates that are functionally linked through structural rearrangements outside of the ion-transport pathway.
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Evidence for a group II intron–like catalytic triplex in the spliceosome pp464 - 471 Sebastian M Fica, Melissa A Mefford, Joseph A Piccirilli and Jonathan P Staley doi:10.1038/nsmb.2815 It has long been thought that the catalytic RNAs of self-splicing group II introns and the spliceosome function by similar mechanisms. Now, a combination of genetic, cross-linking, and biochemical analyses of yeast U6 snRNA provide compelling evidence that spliceosomal RNAs form triplex structures similar to those used by group II introns to catalyze splicing.
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Conformational dynamics of ligand-dependent alternating access in LeuT pp472 - 479 Kelli Kazmier, Shruti Sharma, Matthias Quick, Shahidul M Islam, Benoît Roux et al. doi:10.1038/nsmb.2816 LeuT is a Na+-coupled amino acid transporter that is similar in sequence and function to eukaryotic neurotransmitter/sodium symporters, which are active in reuptake of neurotransmitters from the synapse. Distance measurements between spin-label pairs are used to identify ligand-dependent structural transitions in LeuT.
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T-cell receptor recognition of HLA-DQ2–gliadin complexes associated with celiac disease pp480 - 488 Jan Petersen, Veronica Montserrat, Jorge R Mujico, Khai Lee Loh, Dennis X Beringer et al. doi:10.1038/nsmb.2817 A central event in celiac disease (CD) is the recognition by TCRs of gluten epitopes presented by specific HLAs, with HLA-DQ2 being associated with 95% of CD cases. The molecular basis for these interactions are now revealed by crystal structures of TCRs from individuals with CD in complex with wheat gliadin epitopes presented by HLA-DQ2.
See also: News and Views by Jabri et al.
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Mechanism of activation of bacterial cellulose synthase by cyclic di-GMP pp489 - 496 Jacob L W Morgan, Joshua T McNamara and Jochen Zimmer doi:10.1038/nsmb.2803 Cyclic di-GMP (c-di-GMP) regulates a number of bacterial processes, including synthesis of cellulose during biofilm formation. The PilZ domain from bacterial cellulose synthase BcsA–BcsB senses c-di-GMP and activates the enzyme. Now crystal structures of BcsA–BcsB along with functional analysis reveal that binding of c-di-GMP releases a conserved gating loop to allow substrate to enter the active site.
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Brief Communication | Top |
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Role of polymerase β in complementing aprataxin deficiency during abasic-site base excision repair pp497 - 499 Melike Çaglayan, Vinod K Batra, Akira Sassa, Rajendra Prasad and Samuel H Wilson doi:10.1038/nsmb.2818 5'-adenylated DNA adducts generated during nucleotide excision repair (NER) are removed by aprataxin to permit DNA end ligation. Now, structural and kinetic analyses reveal that NER enzymes DNA polymerase β and FEN1 can also excise these adducts and thus provide a 'backup' repair pathway for abasic sites.
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