scholarly journals Structural investigation of cyclic nucleotide binding proteins from Trypanosoma cruzi

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Gabriel Ferri ◽  
Martin Edreira ◽  
Ivan Campeotto
Keyword(s):  
Life Cycle ◽  
Structural Biology ◽  
Structural Investigation ◽  
Buenos Aires ◽  
Therapeutic Agents ◽  
Parasite Life Cycle ◽  
Structure Based Drug Design ◽  
Antiparasitic Drugs ◽  
Nucleotide Binding Proteins ◽  
Biology Group

Fora targeted therapy of Trypanosomiasis, new antiparasitic drugs should be specifically directed against essential pathways in the parasite life cycle. Among these potential targets are signal transduction pathways, which have remained largely unexplored in Trypanosoma species. Of special interest is cAMP-mediated signaling, since cAMP has been shown to play critical roles in the life cycle of T. cruzi and in host cell during invasion. The presented research focuses on the identification and characterisation of novel cAMP response proteins (CARPs) in T. cruzi by using a multi disciplinary approach involving the parasitology group of Dr Martin Edreira (University of Buenos Aires, Argentina) and the structural biology group of Dr Ivan Campeotto (University of Leicester, UK). The aim of the project is not only to increase our knowledge about T. cruzi biology but also to target CARPs for the design and development of novel therapeutic agents against Chagas disease. To date, protein crystals of one of the members of the CARP family have been obtained, paving the way for structure determination and for a structure-based drug design approach.

The Leishmania promastigote surface antigen 2 complex is differentially expressed during the parasite life cycle

1995 ◽  
Vol 74 (2) ◽  
pp. 189-200 ◽  
Author(s):  
Emanuela Handman ◽  
Amelia H. Osborn ◽  
Fiona Symons ◽  
Rosemary van Driel ◽  
Roberto Cappai
Keyword(s):  
Life Cycle ◽  
Surface Antigen ◽  
Differentially Expressed ◽  
Parasite Life Cycle

scholarly journals Flagellar Motility ofTrypanosoma cruziEpimastigotes

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
G. Ballesteros-Rodea ◽  
M. Santillán ◽  
S. Martínez-Calvillo ◽  
R. Manning-Cela
Keyword(s):  
Life Cycle ◽  
Trypanosoma Cruzi ◽  
Quantitative Description ◽  
Flagellar Motility ◽  
Parasite Life Cycle ◽  
Large Variability ◽  
Rotational Angle ◽  
Ciliary Beating ◽  
Parasite Motility ◽  
Parasite Behavior

The hemoflagellateTrypanosoma cruziis the causative agent of American trypanosomiasis. Despite the importance of motility in the parasite life cycle, little is known aboutT. cruzimotility, and there is no quantitative description of its flagellar beating. Using video microscopy and quantitative vectorial analysis of epimastigote trajectories, we find a forward parasite motility defined by tip-to-base symmetrical flagellar beats. This motion is occasionally interrupted by base-to-tip highly asymmetric beats, which represent the ciliary beat of trypanosomatid flagella. The switch between flagellar and ciliary beating facilitates the parasite's reorientation, which produces a large variability of movement and trajectories that results in different distance ranges traveled by the cells. An analysis of the distance, speed, and rotational angle indicates that epimastigote movement is not completely random, and the phenomenon is highly dependent on the parasite behavior and is characterized by directed and tumbling parasite motion as well as their combination, resulting in the alternation of rectilinear and intricate motility paths.

scholarly journals Encounter rate between local populations shapes host selection in complex parasite life cycle

2006 ◽  
Vol 89 (1) ◽  
pp. 99-106 ◽  
Author(s):  
GÉRALDINE LOOT ◽  
YOUNG-SEUK PARK ◽  
SOVAN LEK ◽  
SÉBASTIEN BROSSE
Keyword(s):  
Life Cycle ◽  
Host Selection ◽  
Encounter Rate ◽  
Parasite Life Cycle ◽  
Local Populations

scholarly journals Structural, functional and computational studies of membrane recognition by Plasmodium Perforin-Like Proteins 1 and 2.

2021 ◽  
Author(s):  
Sophie Williams ◽  
Xiulian Yu ◽  
Tao Ni ◽  
Robert Gilbert ◽  
Phillip Stansfeld
Keyword(s):  
Life Cycle ◽  
Lipid Bilayers ◽  
Membrane Binding ◽  
Binding Activity ◽  
Life Cycles ◽  
Site Directed Mutagenesis ◽  
Parasite Life Cycle ◽  
Dynamics Simulations ◽  
Membrane Recognition

Perforin-like proteins (PLPs) play key roles in the mechanisms associated with parasitic disease caused by apicomplexans such as Plasmodium (malaria) and Toxoplasma. The T. gondii PLP1 (TgPLP1) mediates tachyzoite egress from cells, while the five Plasmodium PLPs carry out various roles in the life cycle of the parasite and with respect to the molecular basis of disease. Here we focus on Plasmodium vivax PLP1 and PLP2 (PvPLP1 and PvPLP2) compared to TgPLP1; PvPLP1 is important for invasion of mammalian hosts by the parasite and establishment of a chronic infection, PvPLP2 is important during the symptomatic blood stage of the parasite life cycle. Determination of the crystal structure of the membrane-binding APCβ domain of PvPLP1 reveals notable differences with that of TgPLP1, which are reflected in its inability to bind lipid bilayers in the way that TgPLP1 and PvPLP2 can be shown to. Molecular dynamics simulations combined with site-directed mutagenesis and functional assays allow a dissection of the binding interactions of TgPLP1 and PvPLP2 on lipid bilayers, and reveal a similar tropism for lipids found enriched in the inner leaflet of the mammalian plasma membrane. In addition to this shared mode of membrane binding PvPLP2 displays a secondary synergistic interaction side-on from its principal bilayer interface. This study underlines the substantial differences between the biophysical properties of the APCβ domains of Apicomplexan PLPs, which reflect their significant sequence diversity. Such differences will be important factors in determining the cell targeting and membrane-binding activity of the different proteins, in their different developmental roles within parasite life cycles.

scholarly journals Furuncular Botfly Myiasis – A Case Report

2018 ◽  
Vol 10 (1) ◽  
pp. 9-11
Author(s):  
Juliana Gao ◽  
Vera Tešić ◽  
Vesna Petronić Rosić
Keyword(s):  
Case Report ◽  
Life Cycle ◽  
South America ◽  
Treatment Options ◽  
Local Population ◽  
Body Cavity ◽  
Parasite Life Cycle ◽  
Susceptible Host ◽  
Dermatobia Hominis ◽  
Blood Sucking

Abstract Botfly myiasis is an infestation of the skin or a body cavity by developing larvae of Dermatobia hominis, one of the most common flies that cause human infestation among the local population, in regions ranging from Mexico into South America and in travelers. The life cycle starts when a female fly glues the eggs to the vector, a blood-sucking arthropod, which carries the unhatched larvae to the susceptible host. A case of furuncular botfly myiasis in an 85 year-old female with recent travel to Belize is presented here to highlight the parasite life cycle and review the different treatment options.

scholarly journals Making the invisible enemy visible

2020 ◽  
Author(s):  
Tristan Croll ◽  
Kay Diederichs ◽  
Florens Fischer ◽  
Cameron Fyfe ◽  
Yunyun Gao ◽  
...  
Keyword(s):  
Life Cycle ◽  
Drug Design ◽  
Structure Determination ◽  
Task Force ◽  
Protein Structures ◽  
Structural Models ◽  
Viral Proteins ◽  
Human Cells ◽  
Structure Based Drug Design ◽  
The Eu

AbstractDuring the COVID-19 pandemic, structural biologists rushed to solve the structures of the 28 proteins encoded by the SARS-CoV-2 genome in order to understand the viral life cycle and enable structure-based drug design. In addition to the 204 previously solved structures from SARS-CoV-1, 548 structures covering 16 of the SARS-CoV-2 viral proteins have been released in a span of only 6 months. These structural models serve as the basis for research to understand how the virus hijacks human cells, for structure-based drug design, and to aid in the development of vaccines. However, errors often occur in even the most careful structure determination - and may be even more common among these structures, which were solved quickly and under immense pressure.The Coronavirus Structural Task Force has responded to this challenge by rapidly categorizing, evaluating and reviewing all of these experimental protein structures in order to help downstream users and original authors. In addition, the Task Force provided improved models for key structures online, which have been used by Folding@Home, OpenPandemics, the EU JEDI COVID-19 challenge and others.

scholarly journals The Malaria Parasite Cyclic GMP-Dependent Protein Kinase Plays a Central Role in Blood-Stage Schizogony

2009 ◽  
Vol 9 (1) ◽  
pp. 37-45 ◽  
Author(s):  
Helen M. Taylor ◽  
Louisa McRobert ◽  
Munira Grainger ◽  
Audrey Sicard ◽  
Anton R. Dluzewski ◽  
...  
Keyword(s):  
Life Cycle ◽  
Protein Kinase ◽  
Cyclic Gmp ◽  
Malaria Parasite ◽  
Kinase Inhibitor ◽  
Blood Stage ◽  
Parasite Life Cycle ◽  
Dependent Protein Kinase ◽  
Asexual Blood Stage ◽  
Dependent Protein

ABSTRACT A role for the Plasmodium falciparum cyclic GMP (cGMP)-dependent protein kinase (PfPKG) in gametogenesis in the malaria parasite was elucidated previously. In the present study we examined the role of PfPKG in the asexual blood-stage of the parasite life cycle, the stage that causes malaria pathology. A specific PKG inhibitor (compound 1, a trisubstituted pyrrole) prevented the progression of P. falciparum schizonts through to ring stages in erythrocyte invasion assays. Addition of compound 1 to ring-stage parasites allowed normal development up to 30 h postinvasion, and segmented schizonts were able to form. However, synchronized schizonts treated with compound 1 for ≥6 h became large and dysmorphic and were unable to rupture or liberate merozoites. To conclusively demonstrate that the effect of compound 1 on schizogony was due to its selective action on PfPKG, we utilized genetically manipulated P. falciparum parasites expressing a compound 1-insensitive PfPKG. The mutant parasites were able to complete schizogony in the presence of compound 1 but not in the presence of the broad-spectrum protein kinase inhibitor staurosporine. This shows that PfPKG is the primary target of compound 1 during schizogony and provides direct evidence of a role for PfPKG in this process. Discovery of essential roles for the P. falciparum PKG in both asexual and sexual development demonstrates that cGMP signaling is a key regulator of both of these crucial life cycle phases and defines this molecule as an exciting potential drug target for both therapeutic and transmission blocking action against malaria.

scholarly journals Altered parasite life-cycle processes characterize Babesia divergens infection in human sickle cell anemia

Haematologica ◽  
2019 ◽  
Vol 104 (11) ◽  
pp. 2189-2199 ◽  
Author(s):  
Jeny R. Cursino-Santos ◽  
Manpreet Singh ◽  
Eric Senaldi ◽  
Deepa Manwani ◽  
Karina Yazdanbakhsh ◽  
...  
Keyword(s):  
Life Cycle ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Parasite Life Cycle ◽  
Babesia Divergens

scholarly journals High-yield monolayer graphene grids for near-atomic resolution cryoelectron microscopy

2019 ◽  
Vol 117 (2) ◽  
pp. 1009-1014 ◽  
Author(s):  
Yimo Han ◽  
Xiao Fan ◽  
Haozhe Wang ◽  
Fang Zhao ◽  
Christopher G. Tully ◽  
...  
Keyword(s):  
Structural Biology ◽  
Structural Investigation ◽  
High Yield ◽  
Monolayer Graphene ◽  
Minimal Amount ◽  
Biological Macromolecules ◽  
Atomic Structures ◽  
Specific Proteins ◽  
Protein Density ◽  
Working Mechanisms

Cryogenic electron microscopy (cryo-EM) has become one of the most powerful techniques to reveal the atomic structures and working mechanisms of biological macromolecules. New designs of the cryo-EM grids—aimed at preserving thin, uniform vitrified ice and improving protein adsorption—have been considered a promising approach to achieving higher resolution with the minimal amount of materials and data. Here, we describe a method for preparing graphene cryo-EM grids with up to 99% monolayer graphene coverage that allows for more than 70% grid squares for effective data acquisition with improved image quality and protein density. Using our graphene grids, we have achieved 2.6-Å resolution for streptavidin, with a molecular weight of 52 kDa, from 11,000 particles. Our graphene grids increase the density of examined soluble, membrane, and lipoproteins by at least 5-fold, affording the opportunity for structural investigation of challenging proteins which cannot be produced in large quantity. In addition, our method employs only simple tools that most structural biology laboratories can access. Moreover, this approach supports customized grid designs targeting specific proteins, owing to its broad compatibility with a variety of nanomaterials.

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