Receptor-ligand and parasite protein-protein interactions inPlasmodium vivax: Analysing rhoptry neck proteins 2 and 4

2018 ◽  
Vol 20 (7) ◽  
pp. e12835 ◽  
Author(s):  
Maritza Bermúdez ◽  
Gabriela Arévalo-Pinzón ◽  
Laura Rubio ◽  
Olivier Chaloin ◽  
Sylviane Muller ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Parasite Protein ◽  
Receptor Ligand

Safety of Total Therapy III for Newly Diagnosed Multiple Myeloma: Preliminary Analysis of 62 Consecutive Patients. Safety of Total Therapy III for Newly Diagnosed Multiple Myeloma: Preliminary Analysis of 62 Consecutive Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1582-1582
Author(s):  
Theresa L. Coetzer ◽  
Sonja B. Lauterbach
Keyword(s):  
Phage Display ◽  
Erythrocyte Membrane ◽  
Protein Interactions ◽  
Preliminary Analysis ◽  
Membrane Skeleton ◽  
Newly Diagnosed ◽  
Protein Protein Interactions ◽  
Parasite Protein ◽  
Aspartyl Aminopeptidase ◽  
T7 Bacteriophage

Abstract Malaria is one of the world’s major health problems, causing millions of deaths every year, primarily in Africa. The disease is caused by Plasmodium parasites, which invade and destroy human erythrocytes. Of the four species infecting humans, Plasmodium falciparum is responsible for the greatest morbidity and mortality burden. The erythrocyte membrane plays a vital role in all aspects of the pathogenic phase of the parasite’s life cycle and the protein-protein interactions between host and parasite are a key focus of research. Spectrin is the main structural protein in the erythrocyte membrane skeleton and phage-display technology was used to probe the interaction between P falciparum peptide fragments and human erythrocyte spectrin. A phage-display library was constructed by isolating mRNA from P falciparum strain FCR-3, which was reverse transcribed using two-base anchored oligodT primers. Linkers facilitating directional cloning were added to the cDNA, followed by insertion into a gene encoding the 10B capsid protein of the T7 bacteriophage vector. The vector was packaged into viral particles and the library amplified using Escherichia coli as a host. The presence and size of inserts were determined by PCR amplification with T7 bacteriophage vector arm specific primers. Human erythrocyte membranes were prepared from whole blood by hypotonic lysis and spectrin was extracted with a low ionic strength buffer and purified by size exclusion chromatography. The protein was biotinylated, immobilized on streptavidin-coated magnetic beads and biopanned against the phage library. Bound phage were eluted and amplified in E coli for three additional rounds of biopanning to eliminate non-specific protein-protein interactions. The P falciparum cDNA inserts of interacting phage were sequenced and compared to the PlasmoDB database. One of the sequences was identified as a putative aminopeptidase (PFI1570c), which has a 30.7% homology to a human aspartyl aminopeptidase, an enzyme catalysing the release of N-terminal amino acids from a peptide. The parasite protein contains a putative transmembrane domain at the C terminal end and is larger than the human form, with an estimated molecular weight of 65 kD. Several features that are critical for enzyme activity are conserved in the P falciparum aminopeptidase. These include twelve amino acids (four histidine, three glutamic acid and five aspartic acid residues), which are involved in the binding of catalytic zinc ions in the active site, as well as a putative N-myristoylation site and phosphorylation sites for casein kinase II and protein kinase C. Interestingly, the peptide fragment that bound to spectrin in the initial phage display screening, corresponds to a 33 amino acid fragment that is not found in the human aspartyl aminopeptidase. This suggests an evolutionary development of the parasite that allows the protease to bind to human spectrin. Mass spectrometry and microarray data from the PlasmoDB database indicate that the protein is present at the erythrocyte membrane and is expressed in all the developmental stages of the parasite’s erythrocytic life cycle. During the trophozoite stage the parasite modifies the erythrocyte membrane to allow transport of nutrients and waste products. The aminopeptidase could cleave spectrin and destabilise the membrane skeleton to facilitate the insertion of parasite protein channels during development. It may also play a role in proteolysis of the skeleton to enable the release of schizonts from infected erythrocytes.

scholarly journals Hotspots in Plasmodium and RBC Receptor-Ligand Interactions: Key Pieces for Inhibiting Malarial Parasite Invasion

2020 ◽  
Vol 21 (13) ◽  
pp. 4729
Author(s):  
Manuel Alfonso Patarroyo ◽  
Jessica Molina-Franky ◽  
Marcela Gómez ◽  
Gabriela Arévalo-Pinzón ◽  
Manuel Elkin Patarroyo
Keyword(s):  
Protein Interactions ◽  
Structural Information ◽  
Binding Protein ◽  
Host Cells ◽  
Malarial Parasite ◽  
Protein Protein Interactions ◽  
Parasite Invasion ◽  
Receptor Ligand ◽  
Ligand Interactions ◽  
Erythrocyte Binding

Protein-protein interactions (IPP) play an essential role in practically all biological processes, including those related to microorganism invasion of their host cells. It has been found that a broad repertoire of receptor-ligand interactions takes place in the binding interphase with host cells in malaria, these being vital interactions for successful parasite invasion. Several trials have been conducted for elucidating the molecular interface of interactions between some Plasmodium falciparum and Plasmodium vivax antigens with receptors on erythrocytes and/or reticulocytes. Structural information concerning these complexes is available; however, deeper analysis is required for correlating structural, functional (binding, invasion, and inhibition), and polymorphism data for elucidating new interaction hotspots to which malaria control methods can be directed. This review describes and discusses recent structural and functional details regarding three relevant interactions during erythrocyte invasion: Duffy-binding protein 1 (DBP1)–Duffy antigen receptor for chemokines (DARC); reticulocyte-binding protein homolog 5 (PfRh5)-basigin, and erythrocyte binding antigen 175 (EBA175)-glycophorin A (GPA).

scholarly journals Cerebral malaria: insights from host-parasite protein-protein interactions

2010 ◽  
Vol 9 (1) ◽  
Author(s):  
Aditya Rao ◽  
Mayil K Kumar ◽  
Thomas Joseph ◽  
Gopalakrishnan Bulusu
Keyword(s):  
Cerebral Malaria ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Parasite Protein ◽  
Host Parasite

scholarly journals Homology-Based Prediction of Potential Protein-Protein Interactions between Human Erythrocytes and Plasmodium falciparum

2015 ◽  
Vol 9 ◽  
pp. BBI.S31880 ◽  
Author(s):  
Gayatri Ramakrishnan ◽  
Narayanaswamy Srinivasan ◽  
Ponnan Padmapriya ◽  
Vasant Natarajan
Keyword(s):  
Plasmodium Falciparum ◽  
Protein Interactions ◽  
Laboratory Experiments ◽  
Host Cells ◽  
Interacting Proteins ◽  
Protein Protein Interactions ◽  
Parasite Protein ◽  
Obligate Intracellular ◽  
Host Parasite Interactions ◽  
Host Parasite

Plasmodium falciparum, a causative agent of malaria, is a well-characterized obligate intracellular parasite known for its ability to remodel host cells, particularly erythrocytes, to successfully persist in the host environment. However, the current levels of understanding from the laboratory experiments on the host-parasite interactions and the strategies pursued by the parasite to remodel host erythrocytes are modest. Several computational means developed in the recent past to predict host-parasite/pathogen interactions have generated testable hypotheses on feasible protein-protein interactions. We demonstrate the utility of protein structure-based protocol in the recognition of potential interacting proteins across P. falciparum and host erythrocytes. In concert with the information on the expression and subcellular localization of host and parasite proteins, we have identified 208 biologically feasible interactions potentially brought about by 59 P. falciparum and 30 host erythrocyte proteins. For selected cases, we have evaluated the physicochemical viability of the predicted interactions in terms of surface complementarity, electrostatic complementarity, and interaction energies at protein interface regions. Such careful inspection of molecular and mechanistic details generates high confidence on the predicted host-parasite protein-protein interactions. The predicted host-parasite interactions generate many experimentally testable hypotheses that can contribute to the understanding of possible mechanisms undertaken by the parasite in host erythrocyte remodeling. Thus, the key protein players recognized in P. falciparum can be explored for their usefulness as targets for chemotherapeutic intervention.

Protein-protein interactions of the p53 family with the Bcl-2 family in hepatocellular carcinoma

2011 ◽  
Vol 49 (08) ◽  
Author(s):  
LC König ◽  
M Meinhard ◽  
C Sandig ◽  
MH Bender ◽  
A Lovas ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Interactions ◽  
Protein Protein Interactions ◽  
P53 Family

Partial Purification of a Specific Plasminogen Activator from Porcine Parotid Glands

1974 ◽  
Vol 31 (03) ◽  
pp. 403-414 ◽  
Author(s):  
Terence Cartwright
Keyword(s):  
Nucleic Acid ◽  
Salivary Glands ◽  
Plasminogen Activator ◽  
Protein Interactions ◽  
Partial Purification ◽  
Protein Protein Interactions ◽  
Parotid Glands ◽  
Two Stage ◽  
Preliminary Characterization ◽  
Specific Inhibitors

SummaryA method is described for the extraction with buffers of near physiological pH of a plasminogen activator from porcine salivary glands. Substantial purification of the activator was achieved although this was to some extent complicated by concomitant extraction of nucleic acid from the glands. Preliminary characterization experiments using specific inhibitors suggested that the activator functioned by a similar mechanism to that proposed for urokinase, but with some important kinetic differences in two-stage assay systems. The lack of reactivity of the pig gland enzyme in these systems might be related to the tendency to protein-protein interactions observed with this material.

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