Evolutionary shift toward protein-based architecture in trypanosomal mitochondrial ribosomes

Science ◽  
2018 ◽  
Vol 362 (6413) ◽  
pp. eaau7735 ◽  
Author(s):  
David J. F. Ramrath ◽  
Moritz Niemann ◽  
Marc Leibundgut ◽  
Philipp Bieri ◽  
Céline Prange ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Trypanosoma Brucei ◽  
Ribosomal Rna ◽  
Atomic Structure ◽  
Sleeping Sickness ◽  
Minimal Set ◽  
Functional Elements ◽  
Mitochondrial Ribosomes ◽  
Protein Components

Ribosomal RNA (rRNA) plays key functional and architectural roles in ribosomes. Using electron microscopy, we determined the atomic structure of a highly divergent ribosome found in mitochondria of Trypanosoma brucei, a unicellular parasite that causes sleeping sickness in humans. The trypanosomal mitoribosome features the smallest rRNAs and contains more proteins than all known ribosomes. The structure shows how the proteins have taken over the role of architectural scaffold from the rRNA: They form an autonomous outer shell that surrounds the entire particle and stabilizes and positions the functionally important regions of the rRNA. Our results also reveal the “minimal” set of conserved rRNA and protein components shared by all ribosomes that help us define the most essential functional elements.

scholarly journals Epitranscriptomics of Mammalian Mitochondrial Ribosomal RNA

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2181
Author(s):  
Ivan Laptev ◽  
Olga Dontsova ◽  
Petr Sergiev
Keyword(s):  
Ribosomal Rna ◽  
Functional Role ◽  
Evolutionary History ◽  
Assembly Process ◽  
Modified Nucleotides ◽  
Rna Molecules ◽  
Mitochondrial Ribosomes ◽  
Mitochondrial Rrna ◽  
Peptidyltransferase Center

Modified nucleotides are present in all ribosomal RNA molecules. Mitochondrial ribosomes are unique to have a set of methylated residues that includes universally conserved ones, those that could be found either in bacterial or in archaeal/eukaryotic cytosolic ribosomes and those that are present exclusively in mitochondria. A single pseudouridine within the mt-rRNA is located in the peptidyltransferase center at a position similar to that in bacteria. After recent completion of the list of enzymes responsible for the modification of mammalian mitochondrial rRNA it became possible to summarize an evolutionary history, functional role of mt-rRNA modification enzymes and an interplay of the mt-rRNA modification and mitoribosome assembly process, which is a goal of this review.

scholarly journals Mechanisms of Arsenical and Diamidine Uptake and Resistance in Trypanosoma brucei

2003 ◽  
Vol 2 (5) ◽  
pp. 1003-1008 ◽  
Author(s):  
Enock Matovu ◽  
Mhairi L. Stewart ◽  
Federico Geiser ◽  
Reto Brun ◽  
Pascal Mäser ◽  
...  
Keyword(s):  
Trypanosoma Brucei ◽  
Drug Sensitivity ◽  
Sleeping Sickness ◽  
Drug Uptake ◽  
Sub Saharan Africa ◽  
Parental Line ◽  
Adenosine Transport ◽  
Sub Saharan ◽  
High Level

ABSTRACT Sleeping sickness, caused by Trypanosoma brucei spp., has become resurgent in sub-Saharan Africa. Moreover, there is an alarming increase in treatment failures with melarsoprol, the principal agent used against late-stage sleeping sickness. In T. brucei, the uptake of melarsoprol as well as diamidines is thought to be mediated by the P2 aminopurine transporter, and loss of P2 function has been implicated in resistance to these agents. The trypanosomal gene TbAT1 has been found to encode a P2-type transporter when expressed in yeast. Here we investigate the role of TbAT1 in drug uptake and drug resistance in T. brucei by genetic knockout of TbAT1. Tbat1-null trypanosomes were deficient in P2-type adenosine transport and lacked adenosine-sensitive transport of pentamidine and melaminophenyl arsenicals. However, the null mutants were only slightly resistant to melaminophenyl arsenicals and pentamidine, while resistance to other diamidines such as diminazene was more pronounced. Nevertheless, the reduction in drug sensitivity might be of clinical significance, since mice infected with tbat1-null trypanosomes could not be cured with 2 mg of melarsoprol/kg of body weight for four consecutive days, whereas mice infected with the parental line were all cured by using this protocol. Two additional pentamidine transporters, HAPT1 and LAPT1, were still present in the null mutant, and evidence is presented that HAPT1 may be responsible for the residual uptake of melaminophenyl arsenicals. High-level arsenical resistance therefore appears to involve the loss of more than one transporter.

scholarly journals Molecular epidemiology of African sleeping sickness

Parasitology ◽  
2009 ◽  
Vol 136 (12) ◽  
pp. 1491-1500 ◽  
Author(s):  
G. HIDE ◽  
A. TAIT
Keyword(s):  
Molecular Epidemiology ◽  
Trypanosoma Brucei ◽  
Sleeping Sickness ◽  
Genetic Interactions ◽  
Detailed Knowledge ◽  
Advantages And Disadvantages ◽  
Animal Trypanosomiasis ◽  
Taxonomic Groups ◽  
Reservoir Hosts

SUMMARYHuman sleeping sickness in Africa, caused by Trypanosoma brucei spp. raises a number of questions. Despite the widespread distribution of the tsetse vectors and animal trypanosomiasis, human disease is only found in discrete foci which periodically give rise to epidemics followed by periods of endemicity A key to unravelling this puzzle is a detailed knowledge of the aetiological agents responsible for different patterns of disease – knowledge that is difficult to achieve using traditional microscopy. The science of molecular epidemiology has developed a range of tools which have enabled us to accurately identify taxonomic groups at all levels (species, subspecies, populations, strains and isolates). Using these tools, we can now investigate the genetic interactions within and between populations of Trypanosoma brucei and gain an understanding of the distinction between human- and nonhuman-infective subspecies. In this review, we discuss the development of these tools, their advantages and disadvantages and describe how they have been used to understand parasite genetic diversity, the origin of epidemics, the role of reservoir hosts and the population structure. Using the specific case of T.b. rhodesiense in Uganda, we illustrate how molecular epidemiology has enabled us to construct a more detailed understanding of the origins, generation and dynamics of sleeping sickness epidemics.

scholarly journals A near atomic structure of the active human apoptosome

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Tat Cheung Cheng ◽  
Chuan Hong ◽  
Ildikó V Akey ◽  
Shujun Yuan ◽  
Christopher W Akey
Keyword(s):  
Electron Microscopy ◽  
Cell Death ◽  
Conformational Changes ◽  
Atomic Structure ◽  
Catalytic Domain ◽  
Nucleotide Exchange ◽  
Cryo Electron Microscopy ◽  
Molecular Framework ◽  
Death Signals

In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease.

scholarly journals The role of cytokines in the pathogenesis and staging of Trypanosoma brucei rhodesiense sleeping sickness

2016 ◽  
Vol 12 (1) ◽  
Author(s):  
Charles D. Kato ◽  
Enock Matovu ◽  
Claire. M. Mugasa ◽  
Ann Nanteza ◽  
Vincent P. Alibu
Keyword(s):  
Trypanosoma Brucei ◽  
Sleeping Sickness ◽  
Trypanosoma Brucei Rhodesiense

Electron Microscopy of Metal-Matrix Composites

1970 ◽  
Vol 28 ◽  
pp. 404-405
Author(s):  
A. Lawley ◽  
M. R. Pinnel ◽  
A. Pattnaik
Keyword(s):  
Electron Microscopy ◽  
Metal Matrix Composites ◽  
Metal Matrix ◽  
Critical Evaluation ◽  
Elastic Behavior ◽  
Matrix Composites ◽  
Directionally Solidified ◽  
Fracture Characteristics ◽  
Broad Program

As part of a broad program on composite materials, the role of the interface on the micromechanics of deformation of metal-matrix composites is being studied. The approach is to correlate elastic behavior, micro and macroyielding, flow, and fracture behavior with associated structural detail (dislocation substructure, fracture characteristics) and stress-state. This provides an understanding of the mode of deformation from an atomistic viewpoint; a critical evaluation can then be made of existing models of composite behavior based on continuum mechanics. This paper covers the electron microscopy (transmission, fractography, scanning microscopy) of two distinct forms of composite material: conventional fiber-reinforced (aluminum-stainless steel) and directionally solidified eutectic alloys (aluminum-copper). In the former, the interface is in the form of a compound and/or solid solution whereas in directionally solidified alloys, the interface consists of a precise crystallographic boundary between the two constituents of the eutectic.

Site of Lysosome Production During Hepatic Injury

1969 ◽  
Vol 27 ◽  
pp. 348-349
Author(s):  
Nalin J. Unakar
Keyword(s):  
Electron Microscopy ◽  
Golgi Apparatus ◽  
Mouse Liver ◽  
Hepatic Injury ◽  
Close Approximation ◽  
Experimental Conditions ◽  
Toxic Injury

The increased number of lysosomes as well as the close approximation of lysosomes to the Golgi apparatus in tissue under variety of experimental conditions is commonly observed. These observations suggest Golgi involvement in lysosomal production. The role of the Golgi apparatus in the production of lysosomes in mouse liver was studied by electron microscopy of liver following toxic injury by CCI4.

On Future Directions in Pathology

1982 ◽  
Vol 40 ◽  
pp. 274-277
Author(s):  
Benjamin F. Trump ◽  
Irene K. Berezesky ◽  
Raymond T. Jones
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Clinical Pathology ◽  
Future Directions ◽  
Diagnostic Pathology ◽  
The Past ◽  
Transmission Electron ◽  
Organ Systems ◽  
The Many

The role of electron microscopy and associated techniques is assured in diagnostic pathology. At the present time, most of the progress has been made on tissues examined by transmission electron microscopy (TEM) and correlated with light microscopy (LM) and by cytochemistry using both plastic and paraffin-embedded materials. As mentioned elsewhere in this symposium, this has revolutionized many fields of pathology including diagnostic, anatomic and clinical pathology. It began with the kidney; however, it has now been extended to most other organ systems and to tumor diagnosis in general. The results of the past few years tend to indicate the future directions and needs of this expanding field. Now, in addition to routine EM, pathologists have access to the many newly developed methods and instruments mentioned below which should aid considerably not only in diagnostic pathology but in investigative pathology as well.

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