scholarly journals Low-complexity domains adhere by reversible amyloid-like interactions between kinked β-sheets

2017 ◽  
Author(s):  
Michael P. Hughes ◽  
Michael R. Sawaya ◽  
Lukasz Goldschmidt ◽  
Jose A. Rodriguez ◽  
Duilio Cascio ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Low Complexity ◽  
Nuclear Pore ◽  
Interacting Protein ◽  
Small Surface ◽  
P Bodies ◽  
Atomic Structures ◽  
Surface Areas ◽  
Rna Binders ◽  
As Stress

AbstractControl of metabolism by compartmentation is a widespread feature of higher cells. Recent studies have focused on dynamic intracellular bodies such as stress granules, P-bodies, nucleoli, and metabolic puncta. These bodies appear as separate phases, some containing reversible, amyloid-like fibrils formed by interactions of low-complexity protein domains. Here we report five atomic structures of segments of low-complexity domains from granule-forming proteins, one determined to 1.1 Å resolution by micro-electron diffraction. Four of these interacting protein segments show common characteristics, all in contrast to pathogenic amyloid: kinked peptide backbones, small surface areas of interaction, and predominate attractions between aromatic side-chains. By computationally threading the human proteome on three of our kinked structures, we identified hundreds of low-complexity segments potentially capable of forming such reversible interactions. These segments are found in proteins as diverse as RNA binders, nuclear pore proteins, keratins, and cornified envelope proteins, consistent with the capacity of cells to form a wide variety of dynamic intracellular bodies.One Sentence SummaryAtomic structures show transient membraneless organelles of cells formed by a new type of protein interaction akin to pathogenic amyloid fibrils.

scholarly journals Atomic structures of low-complexity protein segments reveal kinked β sheets that assemble networks

Science ◽  
2018 ◽  
Vol 359 (6376) ◽  
pp. 698-701 ◽  
Author(s):  
Michael P. Hughes ◽  
Michael R. Sawaya ◽  
David R. Boyer ◽  
Lukasz Goldschmidt ◽  
Jose A. Rodriguez ◽  
...  
Keyword(s):  
Structural Feature ◽  
Amyloid Fibrils ◽  
Low Complexity ◽  
Human Proteome ◽  
Nuclear Pore ◽  
Side Chains ◽  
Atomic Structures ◽  
Β Sheets ◽  
Rna Binders ◽  
Common Structural Feature

Subcellular membraneless assemblies are a reinvigorated area of study in biology, with spirited scientific discussions on the forces between the low-complexity protein domains within these assemblies. To illuminate these forces, we determined the atomic structures of five segments from protein low-complexity domains associated with membraneless assemblies. Their common structural feature is the stacking of segments into kinked β sheets that pair into protofilaments. Unlike steric zippers of amyloid fibrils, the kinked sheets interact weakly through polar atoms and aromatic side chains. By computationally threading the human proteome on our kinked structures, we identified hundreds of low-complexity segments potentially capable of forming such interactions. These segments are found in proteins as diverse as RNA binders, nuclear pore proteins, and keratins, which are known to form networks and localize to membraneless assemblies.

Volumes and Surface Areas: Geometries and Scaling Relationships between Coarse- Grained and Atomic Structures

2014 ◽  
Vol 20 (8) ◽  
pp. 1208-1222 ◽  
Author(s):  
Daniel Flatow ◽  
Sumudu Leelananda ◽  
Aris Skliros ◽  
Andrzej Kloczkowski ◽  
Robert Jernigan
Keyword(s):  
Coarse Grained ◽  
Atomic Structures ◽  
Scaling Relationships ◽  
Surface Areas

Focusing on mRNA Granules and Stalled Polysomes Amidst Diverse Mechanisms Underlying mRNA Transport, mRNA Storage, and Local Translation

2020 ◽  
Author(s):  
Mina N. Anadolu ◽  
Wayne S. Sossin
Keyword(s):  
Protein Synthesis ◽  
Liquid Phase ◽  
Mrna Translation ◽  
Rna Transport ◽  
P Bodies ◽  
Rna Granules ◽  
Mrna Granules ◽  
Transport Particle ◽  
As Stress ◽  
The Individual

In neurons, mRNAs are transported to distal sites to allow for localized protein synthesis. There are many diverse mechanisms underlying this transport. For example, an individual mRNA can be transported in an RNA transport particle that is tailored to the individual mRNA and its associated binding proteins. In contrast, some mRNAs are transported in liquid-liquid phase separated structures called neuronal RNA granules that are made up of multiple stalled polysomes, allowing for rapid initiation-independent production of proteins required for synaptic plasticity. Moreover, neurons have additional types of liquid-liquid phase–separated structures containing mRNA, such as stress granules and P bodies. This chapter discusses the relationships between all of these structures, what proteins distinguish them, and the possible roles they play in the complex control of mRNA translation at distal sites that allow neurons to use protein synthesis to refine their local proteome in many different ways.

scholarly journals Cryo-EM structure of amyloid fibrils formed by the entire low complexity domain of TDP-43

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qiuye Li ◽  
W. Michael Babinchak ◽  
Witold K. Surewicz
Keyword(s):  
Amyloid Fibrils ◽  
Low Complexity ◽  
Structural Features ◽  
Protein Fragments ◽  
Hydrophobic Residues ◽  
Backbone Conformation ◽  
Hydrophobic Amino Acids ◽  
Insight Into ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis and several other neurodegenerative diseases are associated with brain deposits of amyloid-like aggregates formed by the C-terminal fragments of TDP-43 that contain the low complexity domain of the protein. Here, we report the cryo-EM structure of amyloid formed from the entire TDP-43 low complexity domain in vitro at pH 4. This structure reveals single protofilament fibrils containing a large (139-residue), tightly packed core. While the C-terminal part of this core region is largely planar and characterized by a small proportion of hydrophobic amino acids, the N-terminal region contains numerous hydrophobic residues and has a non-planar backbone conformation, resulting in rugged surfaces of fibril ends. The structural features found in these fibrils differ from those previously found for fibrils generated from short protein fragments. The present atomic model for TDP-43 LCD fibrils provides insight into potential structural perturbations caused by phosphorylation and disease-related mutations.

Interference methods of measuring radii of curvature on small surface areas

1972 ◽  
Vol 15 (5) ◽  
pp. 761-762
Author(s):  
E. P. Osmolovskaya ◽  
I. G. Ivanova
Keyword(s):  
Small Surface ◽  
Surface Areas

scholarly journals Proteomic analysis of Dhh1 complexes reveals a role for Hsp40 chaperone Ydj1 in yeast P-body assembly

2015 ◽  
Author(s):  
Gregory A. Cary ◽  
Dani B.N. Vinh ◽  
Patrick May ◽  
Rolf Kuestner ◽  
Aimee M. Dudley
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Active Role ◽  
Low Complexity ◽  
Mitochondrial Rna ◽  
P Bodies ◽  
Glucose Depletion ◽  
Catalytic Rnas ◽  
Rnp Granules

P-bodies (PB) are ribonucleoprotein (RNP) complexes that aggregate into cytoplasmic foci when cells are exposed to stress. While the conserved mRNA decay and translational repression machineries are known components of PB, how and why cells assemble RNP complexes into large foci remain unclear. Using mass spectrometry to analyze proteins immunoisolated with the core PB protein Dhh1, we show that a considerable number of proteins contain low-complexity (LC) sequences, similar to proteins highly represented in mammalian RNP granules. We also show that the Hsp40 chaperone Ydj1, which contains an LC domain and controls prion protein aggregation, is required for the formation of Dhh1-GFP foci upon glucose depletion. New classes of proteins that reproducibly co-enrich with Dhh1-GFP during PB induction include proteins involved in nucleotide or amino acid metabolism, glycolysis, tRNA aminoacylation, and protein folding. Many of these proteins have been shown to form foci in response to other stresses. Finally, analysis of RNA associated with Dhh1-GFP shows enrichment of mRNA encoding the PB protein Pat1 and catalytic RNAs along with their associated mitochondrial RNA-binding proteins, suggesting an active role for RNA in PB function. Thus, global characterization of PB composition has uncovered proteins and RNA that are important for PB assembly.

scholarly journals Intracellular wetting mediates contacts between liquid compartments and membrane-bound organelles

2021 ◽  
Vol 220 (10) ◽  
Author(s):  
Halim Kusumaatmaja ◽  
Alexander I. May ◽  
Roland L. Knorr
Keyword(s):  
Phase Separation ◽  
Membrane Interactions ◽  
Cellular Functions ◽  
P Bodies ◽  
Intracellular Degradation ◽  
Wetting Phenomena ◽  
Membrane Bound ◽  
Membrane Contact ◽  
As Stress ◽  
Protein Rich

Protein-rich droplets, such as stress granules, P-bodies, and the nucleolus, perform diverse and specialized cellular functions. Recent evidence has shown the droplets, which are also known as biomolecular condensates or membrane-less compartments, form by phase separation. Many droplets also contact membrane-bound organelles, thereby functioning in development, intracellular degradation, and organization. These underappreciated interactions have major implications for our fundamental understanding of cells. Starting with a brief introduction to wetting phenomena, we summarize recent progress in the emerging field of droplet–membrane contact. We describe the physical mechanism of droplet–membrane interactions, discuss how these interactions remodel droplets and membranes, and introduce "membrane scaffolding" by liquids as a novel reshaping mechanism, thereby demonstrating that droplet–membrane interactions are elastic wetting phenomena. “Membrane-less” and “membrane-bound” condensates likely represent distinct wetting states that together link phase separation with mechanosensitivity and explain key structures observed during embryogenesis, during autophagy, and at synapses. We therefore contend that droplet wetting on membranes provides a robust and intricate means of intracellular organization.

scholarly journals RNA processing bodies are disassembled during Old World alphavirus infection

2019 ◽  
Vol 100 (10) ◽  
pp. 1375-1389 ◽  
Author(s):  
Lifeng Liu ◽  
Eva Weiss ◽  
Marc D. Panas ◽  
Benjamin Götte ◽  
Stina Sellberg ◽  
...  
Keyword(s):  
Rna Processing ◽  
Nuclear Import ◽  
Semliki Forest Virus ◽  
Early Stage ◽  
Processing Bodies ◽  
Old World ◽  
P Bodies ◽  
Infected Cells ◽  
As Stress ◽  
Alphavirus Infection

RNA processing bodies (P-bodies) are non-membranous cytoplasmic aggregates of mRNA and proteins involved in mRNA decay and translation repression. P-bodies actively respond to environmental stresses, associated with another type of RNA granules, known as stress granules (SGs). Alphaviruses were previously shown to block SG induction at late stages of infection, which is important for efficient viral growth. In this study, we found that P-bodies were disassembled or reduced in number very early in infection with Semliki Forest virus (SFV) or chikungunya virus (CHIKV) in a panel of cell lines. Similar to SGs, reinduction of P-bodies by a second stress (sodium arsenite) was also blocked in infected cells. The disassembly of P-bodies still occurred in non-phosphorylatable eIF2α mouse embryonal fibroblasts (MEFs) that are impaired in SG assembly. Studies of translation status by ribopuromycylation showed that P-body disassembly is independent of host translation shutoff, which requires the phosphorylation of eIF2α in the SFV- or CHIKV-infected cells. Labelling of newly synthesized RNA with bromo-UTP showed that host transcription shutoff correlated with P-body disassembly at the same early stage (3–4 h) after infection. However, inhibition of global transcription with actinomycin D (ActD) failed to disassemble P-bodies as effectively as the viruses did. Interestingly, blocking nuclear import with importazole led to an efficient P-bodies loss. Our data reveal that P-bodies are disassembled independently from SG formation at early stages of Old World alphavirus infection and that nuclear import is involved in the dynamic of P-bodies.

Analysis of Solar Power and Energy Variability Through Site Adaptation of Satellite Data With Quality Controlled Measured Solar Radiation Data

2020 ◽  
Vol 143 (3) ◽  
Author(s):  
Kaviraj Bangarigadu ◽  
Tavish Hookoom ◽  
Yatindra Kumar Ramgolam ◽  
Nadia Foo Kune
Keyword(s):  
Quality Control ◽  
Solar Power ◽  
Winter Season ◽  
Measurement Data ◽  
Control Process ◽  
Small Surface ◽  
Surface Areas ◽  
Quality Control Process ◽  
Winter Peak ◽  
Removal Technique

Abstract Satellite-based solar power data is becoming more and more important because of its continuous temporal and spatial availability. However, its reliability can be enhanced through quality control and calibration against ground-based measurement data. Here, a holistic methodology is employed for the adaptation of satellite-based data for estimating solar energy. For the purpose, high-quality ground-based measurement data and satellite-based datasets are assessed across 12 sites in three small islands located in the Indian Ocean. Initially, both datasets go through a rigorous quality control process. A quantitative analysis of irradiance and insolation data is then conducted. Eventually, site adaptation of satellite-based data is performed using bias removal technique and statistical analysis of datasets. A set of seven statistical performance indicators is used to support the assessment. Analysis of datasets shows that adaptation of peak values should be performed separately. Results showed that despite the small surface areas of the islands studied, a spatial variation of insolation can be depicted. A temporal variation of insolation is also noted with a peak in the summer and low insolation levels in winter. Peak irradiance values tend to exceed solar constant for all sites. Variations of peak irradiance can only be noticed in ground-based measurement data. While insolation levels are comparable in the summer season for all the sites, insolation levels in the winter season are higher in the sites with lower latitudes. Calibration factors for peak irradiance, monthly and annual average irradiance as well as yearly insolation are presented.

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