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Trends in Biochemical Sciences

Pengyu Liu, Auke P Verhaar, Maikel P Peppelenbosch
Ankyrin repeat and suppressor of cytokine signaling (SOCS) box (Asb) proteins are ubiquitin E3 ligases. The subfamily of six-ankyrin repeat domain-containing Asb proteins (Asb5, Asb9, Asb11, and Asb13) is of specific interest because they display unusual strong evolutionary conservation (e.g., urochordate and human ASB11 are >49% similar at the amino acid level) and mediate compartment size expansion, regulating, for instance, the size of the brain and muscle compartment. Thus, they may be involved in the explanation of the differences in brain size between humans and apes...
November 13, 2018: Trends in Biochemical Sciences
Piet Borst, András Váradi, Koen van de Wetering
Ever since Garrod deduced the existence of inborn errors in 1901, a vast array of metabolic diseases has been identified and characterized in molecular terms. In 2018 it is difficult to imagine that there is any uncharted backyard left in the metabolic disease landscape. Nevertheless, it took until 2013 to identify the cause of a relatively frequent inborn error, pseudoxanthoma elasticum (PXE), a disorder resulting in aberrant calcification. The mechanism found was not only biochemically interesting but also points to possible new treatments for PXE, a disease that has remained untreatable...
November 13, 2018: Trends in Biochemical Sciences
Kiran S Gajula
Protein engineering advances, including DNA repair manipulation of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) machinery, have paved the way for the first set of DNA precision base editors (C•G→T•A and A•T→G•C), with wide-ranging implications for treating many human genetic diseases. By utilizing the latest protein evolution advances, a hypothetical model for the first transversion (C•G→G•C) base editor can now be proposed.
November 13, 2018: Trends in Biochemical Sciences
Ping Li, Mingxue Gu, Haoxing Xu
Lysosomes, the degradation center of the cell, are filled with acidic hydrolases. Lysosomes generate nutrient-sensitive signals to regulate the import of H+ , hydrolases, and endocytic and autophagic cargos, as well as the export of their degradation products (catabolites). In response to environmental and cellular signals, lysosomes change their positioning, number, morphology, size, composition, and activity within minutes to hours to meet the changing cellular needs. Ion channels in the lysosome are essential transducers that mediate signal-initiated Ca2+ /Fe2+ /Zn2+ release and H+ /Na+ /K+ -dependent changes of membrane potential across the perimeter membrane...
November 10, 2018: Trends in Biochemical Sciences
Jie Luo, Lu-Yi Jiang, Hongyuan Yang, Bao-Liang Song
Cholesterol is dynamically transported among membrane-bound organelles primarily by nonvesicular mechanisms. Sterol transfer proteins (STPs) bind cholesterol in their hydrophobic pockets and facilitate its transfer across the aqueous cytosol. However, STPs alone may not account for the specific and efficient movement of cholesterol between intracellular membranes. Accumulating evidence has shown that membrane contact sites (MCSs), regions where two distinct organelles are in close apposition to one another, can facilitate STP-mediated cholesterol trafficking in a cell...
November 8, 2018: Trends in Biochemical Sciences
Ariel L Furst, Sarah H Klass, Matthew B Francis
A key challenge in many biological studies is the inability to control the placement of cells in two and three dimensions. As our understanding of the importance of complexity in cellular communities increases, better tools are needed to control the spatial arrangements of cells. One universal method to govern these interactions is DNA hybridization, which relies on the inherent interaction between complementary DNA sequences. DNA hybridization has long been used to assemble complex structures of nanoparticles and more recently has been applied to the complex arrangements of cells...
November 6, 2018: Trends in Biochemical Sciences
Seow Neng Chan, Jun Wei Pek
Intronic sequences are often regarded as 'nonsense' transcripts that are rapidly degraded. We highlight here recent studies on intronic sequences that play regulatory roles as long noncoding RNAs (lncRNAs) which are classified as sisRNAs. Interestingly, sisRNAs come in different forms and are produced via a variety of ways. They regulate genes at the DNA, RNA, and protein levels, and frequently engage in autoregulatory feedback loops to ensure cellular homeostasis under normal and stress conditions. Future directions, evolutionary insights, and potential implications of dysregulated sisRNAs are also discussed, especially in relation to human pathogenesis...
October 31, 2018: Trends in Biochemical Sciences
(no author information available yet)
Operating at the interface of chemical biology, biochemistry, and cell biology, the Baskin Lab develops innovative methods for imaging and probing various classes of lipids and couples these methods to the discovery of novel functions for cellular lipids. Notably, the Baskin Lab has developed a method for imaging the production the signaling lipid phosphatidic acid by phospholipase D enzymes and is applying this method, termed IMPACT, to reveal new biological roles for this lipid second messenger. As well, the Baskin Lab focuses on identifying new roles for inositol-containing phospholipids, or phosphoinositides, in the regulation of developmental and oncogenic signaling by characterizing novel phosphoinositide-binding proteins that act as readers of the membrane bilayer 'phosphoinositide code'...
October 27, 2018: Trends in Biochemical Sciences
Rebecca A Sager, Mark R Woodford, Mehdi Mollapour
New roles for Tsc1 and FNIP1/2 as regulators of the molecular chaperone Hsp90 were recently identified, demonstrating a broader cellular impact outside of AMPK-mTOR signaling. In studying the function of these proteins we must take a holistic view of the cell, instead of maintaining our focus on a single pathway.
October 22, 2018: Trends in Biochemical Sciences
Bharath Raj Madhanagopal, Shunqing Zhang, Esra Demirel, Heitham Wady, Arun Richard Chandrasekaran
Simple base-pairing rules of complementarity, perfected by evolution for encoding genetic information, provide unprecedented control over the process of DNA self-assembly. These rules allow us to build exquisite nanostructures and rationally design their morphology, fine-tune their chemical properties, and program their response to environmental stimuli. DNA nanostructures have emerged as promising candidates for transporting drugs across various physiological barriers of the body. In this review, we discuss the strategies used to transform DNA nanostructures into drug delivery vehicles...
October 17, 2018: Trends in Biochemical Sciences
Elizaveta A Karpova, Reynald Gillet
Great progress has been made toward solving the atomic structure of the ribosome, which is the main biosynthetic machine in cells, but we still do not have a full picture of exactly how cellular ribosomes function. Based on the analysis of crystallographic and electron microscopy data, we propose a basic model of the structural organization of ribosomes into a compartment. This compartment is regularly formed by arrays of ribosomal tetramers made up of two dimers that are actually facing in opposite directions...
October 15, 2018: Trends in Biochemical Sciences
Karen N Allen, Sonya Entova, Leah C Ray, Barbara Imperiali
Monotopic membrane proteins, classified by topology, are proteins that embed into a single face of the membrane. These proteins are generally underrepresented in the Protein Data Bank (PDB), but the past decade of research has revealed new examples that allow the description of generalizable features. This Opinion article summarizes shared characteristics including oligomerization states, modes of membrane association, mechanisms of interaction with hydrophobic or amphiphilic substrates, and homology to soluble folds...
October 15, 2018: Trends in Biochemical Sciences
Xuyu Liu, Marcus J C Long, Yimon Aye
Revolutionary proteomic strategies have enabled rapid profiling of the cellular targets of electrophilic small molecules. However, precise means to directly interrogate how these individual electrophilic modifications at low occupancy functionally reshape signaling networks have until recently been largely limited. We highlight here new methods that transcend proteomic platforms to forge a quantitative link between protein target-selective engagement and downstream signaling. We focus on recent progress in the study of non-enzyme-assisted signaling mechanisms and crosstalk choreographed by native reactive electrophilic species (RES)...
October 13, 2018: Trends in Biochemical Sciences
Xianjun Zhang, Shaowei Dong, Fei Xu
Class Frizzled G protein-coupled receptors (GPCRs), which includes the Smoothened receptor (SMO) and 10 Frizzled receptors (FZDs), are responsible for mediating fundamental signaling in embryonic development and tissue homeostasis. Dysregulation of these receptors can lead to cancer. Structural understanding of these molecules has provided insight to their function and signaling, and guided drug discovery. To date, the structures of the multi- and individual domains of SMO, 14 FZD extracellular domains, and the transmembrane domain (TMD) of FZD4, have been reported...
October 8, 2018: Trends in Biochemical Sciences
Alexandre M Erkine
The transcriptional activation domains (TADs) are critical for life, yet intrinsically disordered polypeptides with no specific consensus sequence, interacting with multiple targets via low-specificity fuzzy contacts. The recent integration of machine learning approaches in biochemistry allows analysis of large experimental datasets of functional TADs as a whole and clear observation of TAD features. The emerging picture describes TADs as sequences without consensus but with a variety of detergent-like mini-motifs enriched in negatively charged and aromatic amino acids...
October 5, 2018: Trends in Biochemical Sciences
Junchao Shi, Yunfang Zhang, Tong Zhou, Qi Chen
tRNA-derived small RNAs (tsRNAs, or tRFs) are a new category of regulatory noncoding RNAs with versatile functions. Recent emerging studies have begun to unveil distinct features of tsRNAs based on their sequence, RNA modifications, and structures that differentially impact their functions towards regulating multiple aspects of translational control and ribosome biogenesis.
October 5, 2018: Trends in Biochemical Sciences
Pablo Fuentes-Prior, Ana Rojas, Arnold T Hagler, Eva Estébanez-Perpiñá
Nuclear receptors (NRs) form homo- and/or heterodimers as central scaffolds of multiprotein complexes, which activate or repress gene transcription to regulate development, homeostasis, and metabolism. Recent studies on NR quaternary structure reveal novel mechanisms of receptor dimerization, the existence of tetrameric chromatin-bound NRs, and previously unanticipated protein-protein/protein-DNA interactions.
October 4, 2018: Trends in Biochemical Sciences
Jinfang Zhang, Fabin Dang, Junming Ren, Wenyi Wei
PD-L1, frequently expressed in human cancers, engages with PD-1 on immune cells and contributes to cancer immune evasion. As such, antibodies blocking the PD-1/PD-L1 interaction reactivate cytotoxic T cells to eradicate cancer cells. However, a majority of cancer patients fail to respond to PD-1/PD-L1 blockade with unclear underlying mechanism(s). Recent studies revealed that PD-L1 expression levels on tumor cells might affect the clinical response to anti-PD-1/PD-L1 therapies. Hence, understanding molecular mechanisms for controlling PD-L1 expression will be important to improve the clinical response rate and efficacy of PD-1/PD-L1 blockade...
October 1, 2018: 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
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
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