Interaction between parasite-encoded JAB1/CSN5 and macrophage migration inhibitory factor proteins attenuates its
Swagata Ghosh1, Laura Ann Leaton1, Laura Farr1
1Department of Medicine, University of Virginia, Charlottesville, Virginia, USA.
Scientific Reports
|July 8, 2018
Summary
Protozoan parasites like Entamoeba histolytica use MIF proteins for immune evasion. Researchers identified a parasite JAB1 protein that binds and inhibits MIF activity, revealing a new regulatory mechanism.
Area of Science:
- Parasitology
- Immunology
- Molecular Biology
Background:
- Protozoans utilize macrophage migration inhibitory factor (MIF) homologs for immune evasion, invasion, and pathogenesis.
- The regulatory mechanisms controlling parasite-encoded MIF activity are not well understood.
Purpose of the Study:
- To identify endogenous parasite proteins that interact with and modulate the activity of Entamoeba histolytica MIF (EhMIF).
- To characterize the interaction between EhMIF and its binding partner and elucidate its functional consequences.
Main Methods:
- Immunoaffinity purification of amebic cell lysate using anti-EhMIF antibody followed by mass spectrometry.
- Confirmation of protein-protein interaction using GST pull-down, co-immunoprecipitation, and Biolayer interferometry (BLI).
- In silico prediction of binding regions and functional assays assessing IL-8 production.
Main Results:
- Amebic JAB1 protein (EhJAB1) was identified as a binding partner for EhMIF.
- Direct interaction between EhMIF and EhJAB1 was confirmed through multiple biochemical assays.
- EhJAB1 binding occurred outside the JAMM deneddylase motif and inhibited EhMIF-induced IL-8 production in human epithelial cells.
Conclusions:
- A parasite-encoded JAB1 protein (EhJAB1) interacts with Entamoeba histolytica MIF (EhMIF).
- EhJAB1 acts as a potential negative regulator of EhMIF activity, impacting host immune responses.
- This discovery provides insights into parasite immune evasion strategies and novel therapeutic targets.
Related Concept Videos
02:42Transcription Attenuation in Prokaryotes
18.5K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
18.5K
01:23Factors Affecting Protein-Drug Binding: Drug Interactions
607
Drug interactions are a critical aspect of pharmacology and can occur when two or more drugs compete for the same binding site. This competition can result in one drug displacing another, altering the effect of the displaced drug. Drug interactions are complex processes that rely heavily on how much of the displacer drug is present and how strongly it can bind to the same sites as the displaced drug.
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
607
01:58Mechanical Protein Functions
5.7K
Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force.
5.7K
01:20Factors Affecting Protein-Drug Binding: Protein-Related Factors
575
Drug binding to proteins is a key aspect of pharmacokinetics and can influence a drug's distribution, absorption, and elimination in the body. Several factors, including the drug's physiochemical properties, protein concentration, disease states, and the number of binding sites on the protein, influence this process.
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be...
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be...
575
01:56Structural Protein Function
30.0K
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity. In bones and teeth, it mineralizes to...
30.0K
02:16Transcription Factors
82.8K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.8K