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Trends in Biochemical Sciences

Zhu Lan, Ming-Yue Lee, Eugene Chun, Bin Liu, Wei Liu
The development of novel biochemical methods to efficiently characterize membrane protein (MP) properties in lipidic cubic phase (LCP) is important for studying complicated MPs and their multimeric complexes. Here, we summarize recent LCP-related assays and provide an outlook on their applications in structure and function studies of MPs.
September 19, 2018: Trends in Biochemical Sciences
Karine Boulay, Ivan Topisirovic, Frédérick A Mallette
Translation plays a crucial role in shaping the proteome during adaptation to various types of stress. A recent study by Gameiro and Struhl identified an inflammatory response which comprises coordination of transcriptional and translational programs, and which appears to be required for recovery from nutrient deprivation.
September 14, 2018: Trends in Biochemical Sciences
Thomas J Nicholls, Claes M Gustafsson
Cells contain thousands of copies of the mitochondrial genome. These genomes are distributed within the tubular mitochondrial network, which is itself spread across the cytosol of the cell. Mitochondrial DNA (mtDNA) replication occurs throughout the cell cycle and ensures that cells maintain a sufficient number of mtDNA copies. At replication termination the genomes must be resolved and segregated within the mitochondrial network. Defects in mtDNA replication and segregation are a cause of human mitochondrial disease associated with failure of cellular energy production...
September 14, 2018: Trends in Biochemical Sciences
Paul E Schavemaker, Bert Poolman
Great progress has been made in elucidating the structural and mechanistic basis of (membrane) protein production. Here, we attempt to look ahead and indicate four directions in which our understanding of the protein production process can grow: (i) determine how the molecular mechanisms influence higher-level processes, such as the distribution of protein copy number over a population of cells or the cell growth rate; (ii) explore the functional landscape that the molecular mechanisms of protein production exist in, for instance by comparing membrane protein insertion mechanisms; (iii) uncover the life history of proteins - that is, what happens to them between their synthesis and degradation; and (iv) determine, and connect by calculation, the numbers that are associated with (membrane) protein production...
September 13, 2018: Trends in Biochemical Sciences
Palanivel Kandasamy, Gergely Gyimesi, Yoshikatsu Kanai, Matthias A Hediger
Amino acid transporters (AATs) are membrane-bound transport proteins that mediate transfer of amino acids into and out of cells or cellular organelles. AATs have diverse functional roles ranging from neurotransmission to acid-base balance, intracellular energy metabolism, and anabolic and catabolic reactions. In cancer cells and diabetes, dysregulation of AATs leads to metabolic reprogramming, which changes intracellular amino acid levels, contributing to the pathogenesis of cancer, obesity and diabetes. Indeed, the neutral amino acid transporters (NATs) SLC7A5/LAT1 and SLC1A5/ASCT2 are likely involved in several human malignancies...
August 31, 2018: Trends in Biochemical Sciences
Yuhkoh Satouh, Masahito Ikawa
Currently, infertility affects ∼16% of couples worldwide. The causes are reported to involve both male and female factors, including fertilization failure between mature spermatozoa and eggs. However, the molecular mechanisms involved in each step of mammalian fertilization are yet to be fully elucidated. Although some of these steps can be rescued with assisted reproductive technologies, it is important to clarify the molecular mechanisms involved for the treatment and diagnosis of infertile couples. This review illustrates recent findings in mammalian fertilization, discovered by combining gene modification techniques with other new approaches, and aims to show how these findings will guide future research in mammalian fertilization...
August 28, 2018: Trends in Biochemical Sciences
Tim Vervliet, David I Yule, Geert Bultynck
Acute pancreatitis is characterized by ATP deficiency and sustained Ca2+ overload in pancreatic acinar cells, leading to premature zymogen activation, auto-digestion of the pancreas, and necrosis. Recent research reveals a rational approach to ameliorate disease through galactose feeding, bypassing hexokinases to restore ATP levels and Ca2+ homeostasis, thereby reducing disease markers.
August 28, 2018: Trends in Biochemical Sciences
Grazia R Tundo, Diego Sbardella, Massimo Coletta
A recently published paper applies cryo-electron microscopy (EM) studies and biochemical/genetic approaches for the elucidation of the mechanisms linking nucleotide binding by ATPases, proteasome conformation dynamics, and gate opening of the 20S core particle. These insights potentially represent a milestone in our understanding of the structural dynamics of the 26S proteasome.
August 22, 2018: Trends in Biochemical Sciences
Hye-Young Sagong, Hyeoncheol Francis Son, So Young Choi, Sang Yup Lee, Kyung-Jin Kim
Polyhydroxyalkanoates (PHAs) are diverse biopolyesters produced by numerous microorganisms and have attracted much attention as a substitute for petroleum-based polymers. Despite several decades of study, the detailed molecular mechanisms of PHA biosynthesis have remained unknown due to the lack of structural information on the key PHA biosynthetic enzyme PHA synthase. The recently determined crystal structure of PHA synthase, together with the structures of acetyl-coenzyme A (CoA) acetyltransferase and reductase, have changed this situation...
August 20, 2018: Trends in Biochemical Sciences
Andrew M James, Cassandra L Smith, Anthony C Smith, Alan J Robinson, Kurt Hoogewijs, Michael P Murphy
Thousands of protein acyl modification sites have now been identified in vivo. However, at most sites the acylation stoichiometry is low, making functional enzyme-driven regulation in the majority of cases unlikely. As unmediated acylation can occur on the surface of proteins when acyl-CoA thioesters react with nucleophilic cysteine and lysine residues, slower nonenzymatic processes likely underlie most protein acylation. Here, we review how nonenzymatic acylation of nucleophilic lysine and cysteine residues occurs; the factors that enhance acylation at particular sites; and the strategies that have evolved to limit protein acylation...
August 18, 2018: Trends in Biochemical Sciences
Raquel Sales Gil, Paola Vagnarelli
Nuclear antigen Ki-67 is widely accepted as a cell proliferation marker in both research and cancer diagnostic settings. Despite its extensive use and clinical value, very little is still known about the biological function of Ki-67. A recent work published in Cell Reports has revealed important novel aspects of Ki-67 regulation that could provide new and extended prognostic and therapeutic value.
August 18, 2018: Trends in Biochemical Sciences
Jacky G Goetz
Established protocols for correlating intravital microscopy with electron microscopy remain cumbersome and mostly rely on a combination of artificial fiducials with anatomical landmarks. A recent study describes a new workflow, achieving label-free 3D correlative light and electron microscopy in the mouse brain.
August 17, 2018: Trends in Biochemical Sciences
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August 8, 2018: Trends in Biochemical Sciences
Matej Vizovišek, Robert Vidmar, Marcin Drag, Marko Fonović, Guy S Salvesen, Boris Turk
Proteases are considered of major importance in biomedical research because of their crucial roles in health and disease. Their ability to hydrolyze their protein and peptide substrates at single or multiple sites, depending on their specificity, makes them unique among the enzymes. Understanding protease specificity is therefore crucial to understand their biology as well as to develop tools and drugs. Recent advancements in the fields of proteomics and chemical biology have improved our understanding of protease biology through extensive specificity profiling and identification of physiological protease substrates...
August 7, 2018: Trends in Biochemical Sciences
Xiao-Wei Wang, Wen-Bin Zhang
Chemical topology has emerged as one intriguing feature in protein engineering. Nature demonstrates the elegance and power of protein topology engineering in the unique biofunctions and exceptional stabilities of cyclotides and lasso peptides. With entangling protein motifs and genetically encoded peptide-protein chemistry, artificial proteins with complex topologies, including cyclic proteins, star proteins, and protein catenanes, have become accessible. Among them, proteins with mechanical bonds ('mechanoproteins') are of special interest, owing to their potential functional benefits such as structure stabilization, quaternary structure control, synergistic multivalency effect, and dynamic mechanical sliding/switching properties...
July 21, 2018: Trends in Biochemical Sciences
Suren A Tatulian
The multiscale models for complex chemical systems constitute a powerful computational tool to describe biomolecular structure and dynamics, including enzymatic reactions. Here, the development of this method is presented as a miraculous chain of events, involving astoundingly lucky encounters of brilliant minds such as Planck, Schrödinger, Pauling, Karplus, Levitt, and Warshel.
June 30, 2018: Trends in Biochemical Sciences
Minna U Kaikkonen, Karen Adelman
Metazoan genomes are broadly transcribed by RNA polymerase II (RNAPII), but surprisingly few of these RNAs encode proteins. Accordingly, there is great interest in understanding the origins and potential roles of the vast array of non-coding RNAs (ncRNAs) that are produced. We present here emerging evidence that the act of transcription and the presence of nascent RNA at a locus is often central to function, rather than specific ncRNA sequences or structures. We highlight examples wherein transcription elongation through a regulatory region modulates chromatin structure and/or transcription factor occupancy, and describe how nascent RNA contributes to the local epigenetic landscape through sequence-independent interactions with chromatin regulators...
September 2018: Trends in Biochemical Sciences
Anna Á Rauscher, Máté Gyimesi, Mihály Kovács, András Málnási-Csizmadia
Blebbistatin is a widely used inhibitor of myosin 2 that enables the study of a broad range of cytoskeleton-related processes. However, blebbistatin has several limitations hindering its applicability: it is fluorescent, poorly water soluble, cytotoxic, and prone to (photo)degradation. Despite these adverse effects, being the only available myosin 2-specific inhibitor, blebbistatin is rather a choice of necessity. Blebbistatin has been modified to improve its properties and some of the new compounds have proven to be useful replacements of the original molecule...
September 2018: Trends in Biochemical Sciences
Anežka Tichá, Blanka Collis, Kvido Strisovsky
The rhomboid superfamily of transmembrane (TM) proteins includes intramembrane serine proteases and several classes of pseudoprotease. Rhomboid-like proteins occur widely across evolution and comprise biologically important regulators of fate of membrane proteins, influencing their proteolysis, trafficking, or degradation. In this review, we discuss how structural and mechanistic insights into the action of rhomboid proteases can inform on the mechanism of the pseudoproteases, and discuss the impact of structural understanding on the development of inhibitors and other chemical biology tools for these proteins...
September 2018: Trends in Biochemical Sciences
Dante M Lepore, Leonora Martínez-Núñez, Mary Munson
A major challenge for a molecular understanding of membrane trafficking has been the elucidation of high-resolution structures of large, multisubunit tethering complexes that spatially and temporally control intracellular membrane fusion. Exocyst is a large hetero-octameric protein complex proposed to tether secretory vesicles at the plasma membrane to provide quality control of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated membrane fusion. Breakthroughs in methodologies, including sample preparation, biochemical characterization, fluorescence microscopy, and single-particle cryoelectron microscopy, are providing critical insights into the structure and function of the exocyst...
September 2018: Trends in Biochemical Sciences
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