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Trends in Biochemical Sciences

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https://www.readbyqxmd.com/read/28442192/structural-insights-into-the-mechanism-of-scanning-and-start-codon-recognition-in-eukaryotic-translation-initiation
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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/28285835/regulation-of-mammalian-mitochondrial-gene-expression-recent-advances
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28254353/bacterial-inclusion-bodies-discovering-their-better-half
#13
REVIEW
Ursula Rinas, Elena Garcia-Fruitós, José Luis Corchero, Esther Vázquez, Joaquin Seras-Franzoso, Antonio Villaverde
Bacterial inclusion bodies (IBs) are functional, non-toxic amyloids occurring in recombinant bacteria showing analogies with secretory granules of the mammalian endocrine system. The scientific interest in these mesoscale protein aggregates has been historically masked by their status as a hurdle in recombinant protein production. However, progressive understanding of how the cell handles the quality of recombinant polypeptides and the main features of their intriguing molecular organization has stimulated the interest in inclusion bodies and spurred their use in diverse technological fields...
February 26, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28254242/do-mammalian-cells-really-need-to-export-and-import-heme
#14
REVIEW
Prem Ponka, Alex D Sheftel, Ann M English, D Scott Bohle, Daniel Garcia-Santos
Heme is a cofactor that is essential to almost all forms of life. The production of heme is a balancing act between the generation of the requisite levels of the end-product and protection of the cell and/or organism against any toxic substrates, intermediates and, in this case, end-product. In this review, we provide an overview of our understanding of the formation and regulation of this metallocofactor and discuss new research on the cell biology of heme homeostasis, with a focus on putative transmembrane transporters now proposed to be important regulators of heme distribution...
February 18, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28202332/cdc20-at-the-crossroads-between-chromosome-segregation-and-mitotic-exit
#15
REVIEW
Maria Kapanidou, Natalie L Curtis, Victor M Bolanos-Garcia
Cell-division cycle protein 20 homologue (Cdc20) has important functions in chromosome segregation and mitotic exit. Cdc20 is the target of the spindle assembly checkpoint (SAC) and a key cofactor of the anaphase-promoting complex or cyclosome (APC/C) E3 ubiquitin ligase, thus regulating APC/C ubiquitin activity on specific substrates for their subsequent degradation by the proteasome. Here we discuss the roles of Cdc20 in SAC signalling and mitotic exit, describe how the integration of traditional approaches with emerging technologies has revealed new details of Cdc20 functions, comment about the potential of Cdc20 as a therapeutic target for the treatment of human malignancies, and discuss recent advances and controversies in the mechanistic understanding of the control of chromosome segregation during cell division...
February 12, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28185716/mitochondrial-complex-ii-at-the-crossroads
#16
REVIEW
Ayenachew Bezawork-Geleta, Jakub Rohlena, Lanfeng Dong, Karel Pacak, Jiri Neuzil
Mitochondrial complex II (CII), also called succinate dehydrogenase (SDH), is a central purveyor of the reprogramming of metabolic and respiratory adaptation in response to various intrinsic and extrinsic stimuli and abnormalities. In this review we discuss recent findings regarding SDH biogenesis, which requires four known assembly factors, and modulation of its enzymatic activity by acetylation, succinylation, phosphorylation, and proteolysis. We further focus on the emerging role of both genetic and epigenetic aberrations leading to SDH dysfunction associated with various clinical manifestations...
February 6, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28314505/how-do-j-proteins-get-hsp70-to-do-so-many-different-things
#17
REVIEW
Elizabeth A Craig, Jaroslaw Marszalek
Hsp70 chaperone machineries have pivotal roles in an array of fundamental biological processes through their facilitation of protein folding, disaggregation, and remodeling. The obligate J-protein co-chaperones of Hsp70s drive much of this remarkable multifunctionality, with most Hsp70s having multiple J-protein partners. Recent data suggest that J-protein-driven versatility is substantially due to precise localization within the cell and the specificity of substrate protein binding. However, this relatively simple view belies the intricacy of J-protein function...
May 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28284537/proteome-scale-human-interactomics
#18
REVIEW
Katja Luck, Gloria M Sheynkman, Ivy Zhang, Marc Vidal
Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics...
May 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28274731/feng-shao-sensing-and-fighting-against-pathogens-from-the-inside
#19
(no author information available yet)
No abstract text is available yet for this article.
April 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28196646/metabolomics-a-primer
#20
REVIEW
Xiaojing Liu, Jason W Locasale
Metabolomics generates a profile of small molecules that are derived from cellular metabolism and can directly reflect the outcome of complex networks of biochemical reactions, thus providing insights into multiple aspects of cellular physiology. Technological advances have enabled rapid and increasingly expansive data acquisition with samples as small as single cells; however, substantial challenges in the field remain. In this primer we provide an overview of metabolomics, especially mass spectrometry (MS)-based metabolomics, which uses liquid chromatography (LC) for separation, and discuss its utilities and limitations...
April 2017: Trends in Biochemical Sciences
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