Cryo-EM structure of 90S small ribosomal subunit precursors in transition states

Science ◽  
2020 ◽  
Vol 369 (6510) ◽  
pp. 1477-1481 ◽  
Author(s):  
Yifei Du ◽  
Weidong An ◽  
Xing Zhu ◽  
Qi Sun ◽  
Jia Qi ◽  
...  
Keyword(s):  
Structural Changes ◽  
Critical Role ◽  
Ribosomal Subunit ◽  
Rna Degradation ◽  
Ribosomal Subunits ◽  
Cryo Electron Microscopy ◽  
Nuclear Exosome ◽  
Assembly Intermediate ◽  
Insight Into

The 90S preribosome is a large, early assembly intermediate of small ribosomal subunits that undergoes structural changes to give a pre-40S ribosome. Here, we gained insight into this transition by determining cryo–electron microscopy structures of Saccharomyces cerevisiae intermediates in the path from the 90S to the pre-40S. The full transition is blocked by deletion of RNA helicase Dhr1. A series of structural snapshots revealed that the excised 5′ external transcribed spacer (5′ ETS) is degraded within 90S, driving stepwise disassembly of assembly factors and ribosome maturation. The nuclear exosome, an RNA degradation machine, docks on the 90S through helicase Mtr4 and is primed to digest the 3′ end of the 5′ ETS. The structures resolved between 3.2- and 8.6-angstrom resolution reveal key intermediates and the critical role of 5′ ETS degradation in 90S progression.

scholarly journals Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs

2018 ◽  
Author(s):  
David M. Kern ◽  
SeCheol Oh ◽  
Richard K. Hite ◽  
Stephen G. Brohawn
Keyword(s):  
Lipid Bilayers ◽  
Critical Role ◽  
Anion Channel ◽  
Lipid Binding ◽  
Channel Structure ◽  
Anion Channels ◽  
Cryo Electron Microscopy ◽  
Lipid Nanodiscs ◽  
Insight Into

AbstractHypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These channels are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A in homo- or hetero-hexameric assemblies. Here we present single-particle cryo-electron microscopy structures of LRRC8A in complex with the inhibitor DCPIB reconstituted in lipid nanodiscs. DCPIB plugs the channel like a cork in a bottle - binding in the extracellular selectivity filter and sterically occluding ion conduction. Constricted and expanded structures reveal coupled dilation of cytoplasmic LRRs and the channel pore, suggesting a mechanism for channel gating by internal stimuli. Conformational and symmetry differences between LRRC8A structures determined in detergent micelles and lipid bilayers related to reorganization of intersubunit lipid binding sites demonstrate a critical role for the membrane in determining channel structure. These results provide insight into LRRC8 gating and inhibition and the role of lipids in the structure of an ionic-strength sensing ion channel.

scholarly journals Mitochondrial ribosome assembly in Neurospora. Structural analysis of mature and partially assembled ribosomal subunits by equilibrium centrifugation in CsCl gradients.

1982 ◽  
Vol 95 (1) ◽  
pp. 267-277 ◽  
Author(s):  
R J Lapolla ◽  
A M Lambowitz
Keyword(s):  
Ribosomal Proteins ◽  
Mitochondrial Protein ◽  
Ribosomal Subunit ◽  
Small Subunit ◽  
Ribosome Assembly ◽  
Ribosomal Subunits ◽  
Mitochondrial Ribosome ◽  
Equilibrium Centrifugation ◽  
Insight Into

In Neurospora, one protein associated with the mitochondrial small ribosomal subunit (S-5, Mr 52,000) is synthesized intramitochondrially and is assumed to be encoded by mtDNA. When mitochondrial protein synthesis is inhibited, either by chloramphenicol or by mutation, cells accumulate incomplete mitochondrial small subunits (CAP-30S and INC-30S particles) that are deficient in S-5 and several other proteins. To gain additional insight into the role of S-5 in mitochondrial ribosome assembly, the structures of Neurospora mitochondrial ribosomal subunits, CAP-30S particles, and INC-30S particles were analyzed by equilibrium centrifugation in CsCl gradients containing different concentrations of Mg+2. The results show (a) that S-5 is tightly associated with small ribosomal subunits, as judged by the fact that it is among the last proteins to be dissociated in CsCl gradients as the Mg+2 concentration is decreased, and (b) that CAP-30S and INC-30S particles, which are deficient in S-5, contain at most 12 proteins that are bound as tightly as in mature small subunits. The CAP-30S particles isolated from sucrose gradients contain a number of proteins that appear to be loosely bound, as judged by dissociation of these proteins in CsCl gradients under conditions in which they remain associated with mature small subunits. The results suggest that S-5 is required for the stable binding of a subset of small subunit ribosomal proteins.

scholarly journals Cryo-EM structures of the DCPIB-inhibited volume-regulated anion channel LRRC8A in lipid nanodiscs

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
David M Kern ◽  
SeCheol Oh ◽  
Richard K Hite ◽  
Stephen G Brohawn
Keyword(s):  
Lipid Bilayers ◽  
Critical Role ◽  
Anion Channel ◽  
Lipid Binding ◽  
Channel Structure ◽  
Anion Channels ◽  
Cryo Electron Microscopy ◽  
Lipid Nanodiscs ◽  
Insight Into

Hypoosmotic conditions activate volume-regulated anion channels in vertebrate cells. These channels are formed by leucine-rich repeat-containing protein 8 (LRRC8) family members and contain LRRC8A in homo- or hetero-hexameric assemblies. Here, we present single-particle cryo-electron microscopy structures of Mus musculus LRRC8A in complex with the inhibitor DCPIB reconstituted in lipid nanodiscs. DCPIB plugs the channel like a cork in a bottle - binding in the extracellular selectivity filter and sterically occluding ion conduction. Constricted and expanded structures reveal coupled dilation of cytoplasmic LRRs and the channel pore, suggesting a mechanism for channel gating by internal stimuli. Conformational and symmetry differences between LRRC8A structures determined in detergent micelles and lipid bilayers related to reorganization of intersubunit lipid binding sites demonstrate a critical role for the membrane in determining channel structure. These results provide insight into LRRC8 gating and inhibition and the role of lipids in the structure of an ionic-strength sensing ion channel.

Science and Theology for Everyone: How Climate Science is Shaping Christianity in the UK

2021 ◽  
Vol 62 (2) ◽  
pp. 147-157
Author(s):  
Caleb Gordon ◽  
Hannah Malcolm
Keyword(s):  
Critical Role ◽  
Climate Science ◽  
Significant Shift ◽  
Christian Life ◽  
Ethical Problems ◽  
Technical Leadership ◽  
Science And Theology ◽  
The Uk ◽  
Insight Into

This article analyses the growing participation of UK Christians in climate initiatives over the last five years. In many cases, climate science is cited as a necessary consideration for the fulfilment of already-existing Christian commitments. This represents a significant shift in the ways UK Christians understand the role of dialogue between theology and the sciences; previous science and theology dialogue has usually been treated as an area of expert concern, primarily offering insight into apologetics or specific ethical problems. By contrast, the dialogue between climate science and theology has seen the emergence of non-technical leadership amid the expectation that climate science plays a critical role in re-examining the meaning of Christian life, both for individuals and as communities.

Persistent Pulmonary Hypertension of the Newborn: Role of Nitric Oxide

1995 ◽  
Vol 10 (6) ◽  
pp. 270-282
Author(s):  
Stella Kourembanas
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Structural Changes ◽  
Critical Role ◽  
Persistent Pulmonary Hypertension ◽  
Cell Contractility ◽  
Vasoactive Mediators ◽  
Nitric Oxide Therapy

Persistent pulmonary hypertension of the newborn (PPHN) is a common cause of respiratory failure in the full-term neonate. Molecular and cellular studies in vascular biology have revealed that endothelial-derived mediators play a critical role in the pathogenesis and treatment of PPHN. Endothelial-derived vasoconstrictors, like endothelin, may increase smooth muscle cell contractility and growth, leading to the physiologic and structural changes observed in the pulmonary arterioles of infants with this disease. On the other hand, decreased production of the endothelial-derived relaxing factor, nitric oxide, may exacerbate pulmonary vasoreactivity and lead to more severe pulmonary hypertension. Exogenous (inhaled) nitric oxide therapy reduces pulmonary vascular resistance and improves oxygenation. The safety and efficacy of this therapy in reducing the need for extracorporeal membrane oxygenation and decreasing long-term morbidity is being tested in several trials nationally and abroad. Understanding the basic mechanisms that regulate the gene expression and production of these vasoactive mediators will lead to improved preventive and therapeutic strategies for PPHN.

scholarly journals Structural consequences of the interaction of RbgA with a 50S ribosomal subunit assembly intermediate

2019 ◽  
Vol 47 (19) ◽  
pp. 10414-10425 ◽  
Author(s):  
Amal Seffouh ◽  
Nikhil Jain ◽  
Dushyant Jahagirdar ◽  
Kaustuv Basu ◽  
Aida Razi ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Large Subunit ◽  
Ribosomal Subunit ◽  
Catalytic Residue ◽  
Gtp Hydrolysis ◽  
Subunit Assembly ◽  
Cryo Electron Microscopy ◽  
Assembly Factor ◽  
Assembly Intermediate ◽  
Immature Particle

Abstract Bacteria harbor a number GTPases that function in the assembly of the ribosome and are essential for growth. RbgA is one of these GTPases and is required for the assembly of the 50S subunit in most bacteria. Homologs of this protein are also implicated in the assembly of the large subunit of the mitochondrial and eukaryotic ribosome. We present here the cryo-electron microscopy structure of RbgA bound to a Bacillus subtilis 50S subunit assembly intermediate (45SRbgA particle) that accumulates in cells upon RbgA depletion. Binding of RbgA at the P site of the immature particle stabilizes functionally important rRNA helices in the A and P-sites, prior to the completion of the maturation process of the subunit. The structure also reveals the location of the highly conserved N-terminal end of RbgA containing the catalytic residue Histidine 9. The derived model supports a mechanism of GTP hydrolysis, and it shows that upon interaction of RbgA with the 45SRbgA particle, Histidine 9 positions itself near the nucleotide potentially acting as the catalytic residue with minimal rearrangements. This structure represents the first visualization of the conformational changes induced by an assembly factor in a bacterial subunit intermediate.

The Cognitive Component of Elite High Jumpers’ Preperformance Routines

2020 ◽  
Vol 34 (2) ◽  
pp. 99-110
Author(s):  
Thomas Gretton ◽  
Lindsey Blom ◽  
Dorice Hankemeier ◽  
Lawrence Judge
Keyword(s):  
Thematic Analysis ◽  
Critical Role ◽  
Valuable Insight ◽  
Psychological Skills ◽  
Cognitive Content ◽  
Successful Performance ◽  
Cognitive Component ◽  
Inductive Thematic Analysis ◽  
Insight Into

Preperformance routines are microlevel performance processes utilized by athletes to facilitate the attainment of an optimal state and enhance the chance for successful performance. Despite continued examination of these routines, only a small proportion of research has been directed toward the cognitive component of these routines. This study explored the cognitive component of elite high jumpers’ preperformance routines, and specifically the consistency of the cognitive content (i.e., psychological skills and strategies). Data were acquired over an 8-week high-jump season and subjected to inductive thematic analysis. Results revealed the consistent implementation of the cognitive content (e.g., visualization) but an inconsistent design of this content (i.e., the content of the visualization). Furthermore, results underline the critical role of high-jump coaches and an athlete’s need to be adaptable and competent in utilizing various types of preperformance routine. This study offers valuable insight into the complexities and inconsistencies of the cognitive component of high jumpers’ preperformance routines.

Local modes

2002 ◽  
Vol 80 (12) ◽  
pp. 1635-1642 ◽  
Author(s):  
Bryan R Henry ◽  
Henrik G Kjaergaard
Keyword(s):  
Atmospheric Chemistry ◽  
Molecular Conformation ◽  
Critical Role ◽  
Historical Background ◽  
Local Mode ◽  
Local Modes ◽  
Band Profile ◽  
Methyl Rotation ◽  
Insight Into

The historical background for the development of the local mode approach is reviewed, including the critical role of the radiation field. The harmonically coupled anharmonic oscillator model is described. Local modes have been used in the interpretation of XH stretching overtone spectra. These spectra can be used as sensitive probes of molecular properties such as bond length and molecular conformation. Examples of these spectral features are discussed. An intensity theory has been developed that permits the accurate calculation of relative and absolute overtone intensities. In molecules with low barriers to methyl rotation, torsional states contribute to the XH stretching band profile. A successful theoretical approach is presented that accounts for these effects and provides insight into the vibrational dynamics. The application of calculated local mode overtone spectra to atmospheric chemistry is discussed.Key words: local mode, overtone, vibrational intensity.

What we have learned from ribosome structures

2008 ◽  
Vol 36 (4) ◽  
pp. 567-574 ◽  
Author(s):  
V. Ramakrishnan
Keyword(s):  
High Resolution ◽  
Ribosomal Subunit ◽  
Ribosomal Subunits ◽  
30S Subunit ◽  
High Resolution Structure ◽  
70S Ribosome ◽  
Year 2000 ◽  
Resolution Structure

The determination of the high-resolution structures of ribosomal subunits in the year 2000 and of the entire ribosome a few years later are revolutionizing our understanding of the role of the ribosome in translation. In the present article, I summarize the main contributions from our laboratory to this worldwide effort. These include the determination of the structure of the 30S ribosomal subunit and its complexes with antibiotics, the role of the 30S subunit in decoding, and the high-resolution structure of the entire 70S ribosome complexed with mRNA and tRNA.

High-Molecular-Weight, High-Unsaturation Copolymers of Isobutylene and Conjugated Dienes. I. Synthesis

1976 ◽  
Vol 49 (4) ◽  
pp. 960-966 ◽  
Author(s):  
W. A. Thaler ◽  
D. J. Buckley
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Cationic Polymerization ◽  
Critical Role ◽  
Conjugated Dienes ◽  
Solution Properties ◽  
Insight Into

Abstract This investigation has provided insight into the critical role of solution properties on the course of cationic polymerization and has led to a technique for reconciling the opposing demands for synthesis of isoolefin-diene copolymers both free from gel and high in molecular weight. By this technique, the synthesis of a broad range of intermediate-unsaturation elastomers of quality has been realized.

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