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Trends in Biochemical Sciences

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https://www.readbyqxmd.com/read/28522328/inhibiting-translation-one-protein-at-a-time
#1
Matthew D Disney
Historically, translational inhibitors have been confined to anti-bacterials that globally affect translation. Lintner et al. demonstrate that small molecules can specifically inhibit translation of a single disease-associated protein by stalling the ribosome's nascent chain [1], opening up a new therapeutic strategy for 'undruggable' proteins.
May 15, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28499500/ca-2-release-channels-join-the-resolution-revolution
#2
REVIEW
Ran Zalk, Andrew R Marks
Ryanodine receptors (RyRs) are calcium release channels expressed in the sarcoendoplasmic reticula of many cell types including cardiac and skeletal muscle cells. In recent years Ca(2+) leak through RyRs has been implicated as a major contributor to the development of diseases including heart failure, muscle myopathies, Alzheimer's disease, and diabetes, making it an important therapeutic target. Recent mammalian RyR1 cryoelectron microscopy (cryo-EM) structures of multiple functional states have clarified longstanding questions including the architecture of the transmembrane (TM) pore and cytoplasmic domains, the location and architecture of the channel gate, ligand-binding sites, and the gating mechanism...
May 9, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28495334/found-in-translation-applying-lessons-from-model-systems-to-strigolactone-signaling-in-parasitic-plants
#3
REVIEW
Shelley Lumba, Asrinus Subha, Peter McCourt
Strigolactones (SLs) are small molecules that act as endogenous hormones to regulate plant development as well as exogenous cues that help parasitic plants to infect their hosts. Given that parasitic plants are experimentally challenging systems, researchers are using two approaches to understand how they respond to host-derived SLs. The first involves extrapolating information on SLs from model genetic systems to dissect their roles in parasitic plants. The second uses chemicals to probe SL signaling directly in the parasite Striga hermonthica...
May 9, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28487210/intrinsically-disordered-proteins-adaptively-reorganize-cellular-matter-during-stress
#4
Sreenivas Chavali, Alexander Gunnarsson, M Madan Babu
Intrinsically disordered proteins (IDPs) can protect cells from diverse stresses by forming higher order assemblies such as reversible aggregates or granules. Recently, Boothby et al. show that IDPs protect tardigrades against desiccation by forming a glass-like amorphous matrix, highlighting that material properties of disordered proteins can confer adaptation during stress.
May 6, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28483377/most-alternative-isoforms-are-not-functionally-important
#5
LETTER
Michael L Tress, Federico Abascal, Alfonso Valencia
No abstract text is available yet for this article.
May 5, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28483376/the-relationship-between-alternative-splicing-and-proteomic-complexity
#6
LETTER
Benjamin J Blencowe
No abstract text is available yet for this article.
May 5, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28483375/mechanisms-regulating-prc2-recruitment-and-enzymatic-activity
#7
REVIEW
Daniel Holoch, Raphaël Margueron
Polycomb repressive complex 2 (PRC2) and its histone H3 lysine-27 methylation activity are crucial for multicellular development by virtue of their role in maintaining transcriptional repression patterns. The recruitment and enzymatic activity of PRC2 are controlled by a series of intricate mechanisms whose molecular details have been emerging at a rapid pace. Recent studies have uncovered intriguing modes of PRC2 regulation by facultative PRC2 subunits, PRC1, and specific features of the chromatin environment...
May 5, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28442192/structural-insights-into-the-mechanism-of-scanning-and-start-codon-recognition-in-eukaryotic-translation-initiation
#8
REVIEW
Alan G Hinnebusch
Initiation of translation on eukaryotic mRNAs generally follows the scanning mechanism, wherein a preinitiation complex (PIC) assembled on the small (40S) ribosomal subunit and containing initiator methionyl tRNAi (Met-tRNAi) scans the mRNA leader for an AUG codon. In a current model, the scanning PIC adopts an open conformation and rearranges to a closed state, with fully accommodated Met-tRNAi, upon AUG recognition. Evidence from recent high-resolution structures of PICs assembled with different ligands supports this model and illuminates the molecular functions of eukaryotic initiation factors eIF1, eIF1A, and eIF2 in restricting to AUG codons the transition to the closed conformation...
April 22, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28438387/structural-insights-into-the-mechanism-of-group-ii-intron-splicing
#9
REVIEW
Chen Zhao, Anna Marie Pyle
While the major architectural features and active-site components of group II introns have been known for almost a decade, information on the individual stages of splicing has been lacking. Recent advances in crystallography and cryo-electron microscopy (cryo-EM) have provided major new insights into the structure of intact lariat introns. Conformational changes that mediate the steps of splicing and retrotransposition are being elucidated, revealing the dynamic, highly coordinated motions that are required for group II intron activity...
April 21, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28416269/dna-protein-crosslink-proteolysis-repair
#10
REVIEW
Bruno Vaz, Marta Popovic, Kristijan Ramadan
Proteins that are covalently bound to DNA constitute a specific type of DNA lesion known as DNA-protein crosslinks (DPCs). DPCs represent physical obstacles to the progression of DNA replication. If not repaired, DPCs cause stalling of DNA replication forks that consequently leads to DNA double-strand breaks, the most cytotoxic DNA lesion. Although DPCs are common DNA lesions, the mechanism of DPC repair was unclear until now. Recent work unveiled that DPC repair is orchestrated by proteolysis performed by two distinct metalloproteases, SPARTAN in metazoans and Wss1 in yeast...
April 14, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28389126/pro-moting-the-turnover-of-gluconeogenic-enzymes-by-a-new-branch-of-the-n-end-rule-pathway
#11
David A Dougan
The N-end rule pathway is a set of protein degradation systems that link the in vivo stability of a protein to its N-terminal residue. A recent paper from Alexander Varshavsky's laboratory [1] identifies a new branch of the N-end rule pathway that specifically recognizes the N-terminal Pro residue of key gluconeogenesis enzymes.
April 4, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28385393/how-scientists-can-become-entrepreneurs
#12
Jonathan N Thon, Sven Karlsson
Translating basic research discoveries through entrepreneurship must be scientist driven and institutionally supported to be successful (not the other way around). Here, we describe why scientists should engage in entrepreneurship, where institutional support for scientist-founders falls short, and how these challenges can be overcome.
April 3, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28372857/functional-actin-networks-under-construction-the-cooperative-action-of-actin-nucleation-and-elongation-factors
#13
REVIEW
Orit Siton-Mendelson, Anne Bernheim-Groswasser
Cells require actin nucleation factors to catalyze the formation of actin networks and elongation factors to control the rate and extent of actin polymerization. Earlier models suggested that the different factors assemble actin networks independently. However, recent evidence indicates that the assembly of most cellular networks involves multiple nucleation and elongation factors that work in concert. Here, we describe how these different factors cooperate, directly or indirectly, to promote the assembly of functional actin network in cells, both in the cytoplasm and nucleoplasm...
March 31, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28363673/lipids-can-make-them-stick-together
#14
Cedric Govaerts
To be active, membrane proteins often need to assemble into multimers either transiently or permanently. Using high-end mass spectrometry (MS), Robinson and colleagues show that the formation of transient multimers may require lipids at the interface while stable oligomers appear not to require such help.
March 28, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28318966/structural-biology-of-the-zika-virus
#15
REVIEW
Yi Shi, George F Gao
Zika virus (ZIKV), a Flaviviridae family member transmitted to humans by mosquitoes, has emerged as a major health concern. ZIKV infections can cause serious neurological complications in adults, and infection in pregnant women can cause congenital malformations, including fetal and newborn microcephaly. In response to this emerging concern, the structural virology field was quick to explore the features of ZIKV. These efforts have provided significant insights into ZIKV pathogenesis, and have identified targets for drug design...
March 15, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28473179/p38%C3%AE-and-p38%C3%AE-from-spectators-to-key-physiological-players
#16
REVIEW
Ana Cuenda, Juan José Sanz-Ezquerro
Although the physiological roles of p38γ and p38δ signalling pathways are largely unknown, new genetic and pharmacological tools are providing groundbreaking information on the function of these two stress-activated protein kinases. Recent studies show the importance of p38γ and p38δ in the regulation of processes as diverse as cytokine production, protein synthesis, exocytosis, cell migration, gene expression, and neuron activity, which have an acute impact on the development of pathologies related to inflammation, diabetes, neurodegeneration, and cancer...
March 11, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28285835/regulation-of-mammalian-mitochondrial-gene-expression-recent-advances
#17
REVIEW
Sarah F Pearce, Pedro Rebelo-Guiomar, Aaron R D'Souza, Christopher A Powell, Lindsey Van Haute, Michal Minczuk
Perturbation of mitochondrial DNA (mtDNA) gene expression can lead to human pathologies. Therefore, a greater appreciation of the basic mechanisms of mitochondrial gene expression is desirable to understand the pathophysiology of associated disorders. Although the purpose of the mitochondrial gene expression machinery is to provide only 13 proteins of the oxidative phosphorylation (OxPhos) system, recent studies have revealed its remarkable and unexpected complexity. We review here the latest breakthroughs in our understanding of the post-transcriptional processes of mitochondrial gene expression, focusing on advances in analyzing the mitochondrial epitranscriptome, the role of mitochondrial RNA granules (MRGs), the benefits of recently obtained structures of the mitochondrial ribosome, and the coordination of mitochondrial and cytosolic translation to orchestrate the biogenesis of OxPhos complexes...
March 9, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28274732/flavins-as-covalent-catalysts-new-mechanisms-emerge
#18
REVIEW
Valentina Piano, Bruce A Palfey, Andrea Mattevi
With approximately 1% of proteins being flavoproteins, flavins are at the heart of a plethora of redox reactions in all areas of biology. Thanks to a series of fascinating recent discoveries, in addition to redox chemistry, covalent catalysis is now being recognized more frequently as a common strategy in flavoenzymes, with unprecedented mechanisms becoming apparent. Thus, noncanonical covalent reactions by flavins are emerging as a new pervasive concept in basic enzymology and biochemistry. These diverse enzymes are engaged in most biological processes, positioning the knowledge being gained from these new mechanisms to be translated into drugs that function through covalent mechanisms...
March 5, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28268045/mechanisms-governing-precise-protein-biotinylation
#19
REVIEW
Louise M Sternicki, Kate L Wegener, John B Bruning, Grant W Booker, Steven W Polyak
Protein biotinylation is a key post-translational modification found throughout the living world. The covalent attachment of a biotin cofactor onto specific metabolic enzymes is essential for their activity. This modification is distinctive, in that it is carried out by a single enzyme: biotin protein ligase (BPL), an enzyme that is able to biotinylate multiple target substrates without aberrant-off target biotinylation. BPL achieves this target selectivity by recognizing a sequence motif in the context of a highly conserved tertiary structure...
March 3, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28268044/deciphering-the-mrnp-code-rna-bound-determinants-of-post-transcriptional-gene-regulation
#20
REVIEW
Niels H Gehring, Elmar Wahle, Utz Fischer
Eukaryotic cells determine the final protein output of their genetic program not only by controlling transcription but also by regulating the localization, translation and turnover rates of their mRNAs. Ultimately, the fate of any given mRNA is determined by the ensemble of all associated RNA-binding proteins (RBPs), non-coding RNAs and metabolites collectively known as the messenger ribonucleoprotein particle (mRNP). Although many mRNA-associated factors have been identified over the past years, little is known about the composition of individual mRNPs and the cooperation of their constituents...
March 3, 2017: Trends in Biochemical Sciences
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