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Current Opinion in Structural Biology

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https://www.readbyqxmd.com/read/30219656/membrane-protein-structural-biology-in-the-era-of-single-particle-cryo-em
#1
REVIEW
Yifan Cheng
In the past few years, significant technological breakthroughs in single particle cryo-electron microscopy enabled a 'resolution revolution' of this technique. It also changed structural biology in an unprecedented way. For many biological macromolecules, obtaining well-ordered crystals of suitable size is no longer a prerequisite for determining their atomic structures. One of the most impacted areas is the structural biology of integral membrane proteins. New structures are now determined at a rapid pace...
September 13, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30218786/a-structural-view-of-the-initiators-for-chromosome-replication
#2
REVIEW
Kin Fan On, Matt Jaremko, Bruce Stillman, Leemor Joshua-Tor
No abstract text is available yet for this article.
September 12, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30205262/molecular-modeling-of-conformational-dynamics-and-its-role-in-enzyme-evolution
#3
REVIEW
Petrović Dušan, Kamerlin Shina Caroline Lynn
With increasing computational power, biomolecular simulations have become an invaluable tool for understanding enzyme mechanisms and the origins of enzyme catalysis. More recently, computational studies have started to focus on understanding how enzyme activity itself evolves, both in terms of enhancing the native or new activities on existing enzyme scaffolds, or completely de novo on previously non-catalytic scaffolds. In this context, both experiment and molecular modeling provided strong evidence for an important role of conformational dynamics in the evolution of enzyme functions...
September 8, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30173121/a-structural-perspective-on-tail-anchored-protein-biogenesis-by-the-get-pathway
#4
REVIEW
Agnieszka Mateja, Robert J Keenan
Many tail-anchored (TA) membrane proteins are targeted to and inserted into the endoplasmic reticulum (ER) by the `guided entry of tail-anchored proteins' (GET) pathway. This post-translational pathway uses transmembrane-domain selective cytosolic chaperones for targeting, and a dedicated membrane protein complex for insertion. The past decade has seen rapid progress towards defining the molecular basis of TA protein biogenesis by the GET pathway. Here we review the mechanisms underlying each step of the pathway, emphasizing recent structural work and highlighting key questions that await future studies...
August 30, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30172766/ribonucleoprotein-particles-advances-and-challenges-in-computational-methods
#5
REVIEW
Shlomi Dvir, Amir Argoetti, Yael Mandel-Gutfreund
RNA-binding proteins (RBPs) interact with RNA to form Ribonucleoprotein Particles (RNPs). The interaction between RBPs and their RNA partners are traditionally thought to be mediated by highly conserved RNA-binding domains (RBDs). Recently, high-throughput studies led to the discovery of hundreds of novel proteins and domains, of which many do not follow the classical definition of RNA-binding. Despite technological innovations, experimental screenings are currently limited to the detection of specific types of RNPs, underscoring the importance of computational methods for predicting novel RBPs and RNA interacting residues and interfaces...
August 30, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30172081/motif-models-for-rna-binding-proteins
#6
REVIEW
Alexander Sasse, Kaitlin U Laverty, Timothy R Hughes, Quaid D Morris
Identifying the binding preferences of RNA-binding proteins (RBPs) is important in understanding their contribution to post-transcriptional regulation. Here, we review the current state-of-the art of RNA motif identification tools for RBPs. New in vivo and in vitro data sets provide sufficient statistical power to enable detection of relatively long and complex sequence and sequence-structure binding preferences, and recent computational methods are geared towards quantitative identification of these patterns...
August 29, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30125772/advances-in-cryoem-and-its-impact-on-%C3%AE-pore-forming-proteins
#7
REVIEW
Courtney M Boyd, Doryen Bubeck
Deployed by both hosts and pathogens, β-pore-forming proteins (β-PFPs) rupture membranes and lyse target cells. Soluble protein monomers oligomerize on the lipid bilayer where they undergo dramatic structural rearrangements, resulting in a transmembrane β-barrel pore. Advances in electron cryo-microscopy (cryoEM) sample preparation, image detection, and computational algorithms have led to a number of recent structures that reveal a molecular mechanism of pore formation in atomic detail.
August 17, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30121401/enzyme-action-at-rna-protein-interface-in-dtd-like-fold
#8
REVIEW
Satya Brata Routh, Rajan Sankaranarayanan
The contemporary `RNA-protein world' is exemplified by close associations between many RNAs and proteins which are necessary to carry out important biological processes. DTD-like fold, which is involved in translational proofreading, represents such RNA-protein complexes (RNPCs). Interestingly, it interacts with the substrates in the active site mostly through the main chain, and side chains are dispensable for both substrate specificity and catalysis. It functions at the RNA-protein interface to perform RNA-based catalysis using the 2'-OH of adenosine-76 of tRNA...
August 16, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30103204/from-the-resolution-revolution-to-evolution-structural-insights-into-the-evolutionary-relationships-between-vesicle-coats-and-the-nuclear-pore
#9
REVIEW
Martin Beck, Shyamal Mosalaganti, Jan Kosinski
Nuclear pores and coated vesicles are elaborate multi-component protein complexes that oligomerize on membranes, and stabilize or induce membrane curvature. Their components, nucleoporins and coat proteins, respectively, share similar structural folds and some principles of how they interact with membranes. The protocoatomer hypothesis postulates that this is due to divergent evolution from a common ancestor. It therefore has been suggested that nucleoporins and coat proteins have similar higher order architectures...
August 10, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30096461/beyond-structures-of-highly-symmetric-purified-viral-capsids-by-cryo-em
#10
REVIEW
Robert Stass, Serban L Ilca, Juha T Huiskonen
Cryogenic transmission electron microscopy (cryo-EM) is widely used to determine high-resolution structures of symmetric virus capsids. The method holds promise for extending studies beyond purified capsids and their symmetric protein shells. The non-symmetric genome component has been addressed in dsRNA cypoviruses and ssRNA bacteriophages Qβ and MS2. The structure of human herpes simplex virus type 1 capsids has been determined within intact virions to resolve capsid-tegument interactions. Electron tomography under cryogenic conditions (cryo-ET), has allowed resolving an early membrane fusion intermediate of Rift Valley fever virus...
August 7, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30059805/allosteric-activation-of-raf-in-the-mapk-signaling-pathway
#11
REVIEW
Chung-Jung Tsai, Ruth Nussinov
Protein kinases are evolutionarily crafted into two functional states. In response to stimuli, kinase, which is usually populated in an inactive state, becomes active. Here, we outline a unified scheme to explain how kinases are activated physiologically and pathologically, focusing on RAF allosteric activation. Key concepts include the population shift from the inactive to the active state is relative; the relative populations are altered additively via allosteric events; and the structural features of the active conformation are coupled with the regulatory and catalytic spines to align the catalytic sequence motifs...
July 27, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30056307/single-particle-cryo-em-an-optimal-tool-to-study-cytoskeletal-proteins
#12
REVIEW
Sabrina Pospich, Stefan Raunser
Cytoskeletal proteins play essential roles in many cellular processes. Knowledge of their structures is important to understand their function and regulation. Since cytoskeletal polymers are difficult to crystallize, cryo-EM has been the predominant method of choice to study their structures. Recent advances in the methodology have enabled reconstructions at near-atomic resolution. In this review, we focus on novel insights gained from high-resolution cryo-EM structures of cytoskeletal polymers. These include eukaryotic proteins such as F-actin and microtubules as well as their prokaryotic homologues...
July 26, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30055347/reprogramming-g-protein-coupled-receptor-structure-and-function
#13
REVIEW
D Keri, P Barth
The prominence of G protein-coupled receptors (GPCRs) in human physiology and disease has resulted in their intense study in various fields of research ranging from neuroscience to structural biology. With over 800 members in the human genome and their involvement in a myriad of diseases, GPCRs are the single largest family of drug targets, and an ever-present interest exists in further drug discovery and structural characterization efforts. However, low GPCR expression and stability outside the natural lipid environments have challenged these efforts...
July 25, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30048836/microscopic-view-of-lipids-and-their-diverse-biological-functions
#14
REVIEW
Po-Chao Wen, Paween Mahinthichaichan, Noah Trebesch, Tao Jiang, Zhiyu Zhao, Eric Shinn, Yuhang Wang, Mrinal Shekhar, Karan Kapoor, Chun Kit Chan, Emad Tajkhorshid
Biological membranes and their diverse lipid constituents play key roles in a broad spectrum of cellular and physiological processes. Characterization of membrane-associated phenomena at a microscopic level is therefore essential to our fundamental understanding of such processes. Due to the semi-fluid and dynamic nature of lipid bilayers, and their complex compositions, detailed characterization of biological membranes at an atomic scale has been refractory to experimental approaches. Computational modeling and simulation offer a highly complementary toolset with sufficient spatial and temporal resolutions to fill this gap...
July 23, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30031306/detecting-and-interpreting-dna-methylation-marks
#15
REVIEW
Ren Ren, John R Horton, Xing Zhang, Robert M Blumenthal, Xiaodong Cheng
The generation, alteration, recognition, and erasure of epigenetic modifications of DNA are fundamental to controlling gene expression in mammals. These covalent DNA modifications include cytosine methylation by AdoMet-dependent methyltransferases and 5-methylcytosine oxidation by Fe(II)-dependent and α-ketoglutarate-dependent dioxygenases. Sequence-specific transcription factors are responsible for interpreting the modification status of specific regions of chromatin. This review focuses on recent developments in characterizing the functional and structural links between the modification status of two DNA bases: 5-methylcytosine and 5-methyluracil (thymine)...
July 19, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30015201/ribosomes-and-cryo-em-a-duet
#16
REVIEW
Alan Brown, Sichen Shao
Ribosomes and electron cryomicroscopy (cryo-EM) share a long, intertwined history. However, cryo-EM only recently usurped X-ray crystallography as the predominant structural method to study ribosomes in atomic detail. The main, but not only, reason for this succession was the introduction of direct-electron detectors enabling cryo-EM to achieve equally high resolutions. Here, we describe how cryo-EM sample preparation and data processing allows new types of structural analyses not possible by X-ray crystallography...
July 14, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30015202/the-cryo-em-resolution-revolution-and-transcription-complexes
#17
REVIEW
Jonas Hanske, Yashar Sadian, Christoph W Müller
Direct electron detector technology combined with improved imaging processing procedures has dramatically increased the resolution that can be obtained by single-particle cryo-electron microscopy and cryo-electron tomography. These developments-often referred to as the `resolution revolution' in cryo-EM-have had a profound impact on the structural biology of transcription as they allow the determination of atomic or near-atomic resolution structures of very large, flexible and often transient transcription complexes that in many cases had resisted crystal structure determination for decades...
July 12, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/30005324/eukaryotic-dna-polymerases
#18
REVIEW
Rinku Jain, Aneel K Aggarwal, Olga Rechkoblit
The eukaryotic DNA replication machinery is conserved from yeast to humans and requires the actions of multiple DNA polymerases. In addition to replicative DNA polymerases for duplication of the leading and lagging DNA strands, another group of specialized polymerases is required for DNA repair and/or translesion DNA synthesis (TLS). We emphasize here recent findings that accelerate our understanding of the structure and mechanisms of these remarkable enzymes. We also highlight growing evidence on the role of DNA polymerases in the origin of certain cancers, and paradoxically as emerging targets for cancer therapy...
July 10, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29990672/two-distinct-transcriptional-controls-triggered-by-nuclear-piwi-piriscs-in-the-drosophila-pirna-pathway
#19
REVIEW
Kaoru Sato, Mikiko C Siomi
Transposons occupy a large proportion of eukaryotic genomes. Spontaneous movement of transposons within the genome leads to genomic mutations that are often life threatening. To avoid such outcomes, host species have acquired an elaborate molecular pathway during evolution, in which PIWI proteins and PIWI-interacting RNAs (piRNAs) collaboratively control transposons to maintain germline genome integrity. Studies of PIWI-piRNA-based transposon silencing have uncovered the molecular mechanisms underlying piRNA biogenesis and the silencing mode-of-action in the pathway...
July 7, 2018: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/29980106/metal-chelating-non-canonical-amino-acids-in-metalloprotein-engineering-and-design
#20
REVIEW
Patrick J Almhjell, Jeremy H Mills
The ability to rationally design metalloproteins with desired functions remains a difficult challenge despite many years of effort. Recently, the potential of using genetically encoded metal-chelating non-canonical amino acids (NCAAs) to circumvent longstanding difficulties in this field has begun to be explored. In this review, we describe the development of this approach and its application to the rational design or directed evolution of NCAA-containing metalloproteins in which the bound metal ions serve in structural roles, as catalysts, or as regulators of the assembly or disassembly of protein complexes...
July 3, 2018: Current Opinion in Structural Biology
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