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Characterization of a putative nuclear receptor from Onchocerca volvulus
T R Unnasch1, J Bradley, J Beauchamp
1University of Alabama at Birmingham, Division of Geographic Medicine, 35294-2170, USA. trunnasch@geomed.dom.uab.edu
Abstract:
Steroids and retinoids are important regulators of development in invertebrates and vertebrates. The central mediators of action of these compounds are their cognate receptors, which together form a family of proteins known as the nuclear receptor family. Previous studies have demonstrated that the genome of Onchocerca volvulus encodes at least three members of the nuclear receptor family. Here, the characterization of one member of this family from O. volvulus, designated OvNR-2, is described. OvNR-2 was found to be most similar to a number of vertebrate retinoic acid receptors and to the Drosophila melanogaster EiP78c protein. Modeling studies suggest that OvNR-2 forms a boot shaped ligand-binding cavity of a shape and size that can bind steroids. Expression of the mRNA corresponding to OvNR-2 is tightly regulated in adult parasites, appearing only in the extended intrauterine microfilariae. The protein derived from expression of the OvNR-2 cDNA in a bacterial system is recognized by serum antibodies in a majority of individuals infected with O. volvulus.
Insights
Researchers characterized OvNR-2, a nuclear receptor from Onchocerca volvulus. This protein, potentially binding steroids, is expressed in microfilariae and recognized by infected host antibodies.
Area of Science:
- Molecular biology
- Parasitology
- Biochemistry
Background:
- Steroids and retinoids are crucial developmental regulators in many organisms.
- Nuclear receptors mediate the actions of steroids and retinoids.
- The Onchocerca volvulus genome contains at least three nuclear receptor family members.
Purpose of the Study:
- To characterize a specific nuclear receptor member, OvNR-2, from Onchocerca volvulus.
- To investigate the structural and functional properties of OvNR-2.
- To determine the expression pattern and immunogenicity of OvNR-2.
Main Methods:
- Sequence analysis and homology comparison.
- Molecular modeling of the ligand-binding domain.
- mRNA expression analysis using RT-PCR.
- Bacterial expression of OvNR-2 cDNA and antibody recognition assays.
Main Results:
- OvNR-2 shows similarity to vertebrate retinoic acid receptors and Drosophila EiP78c.
- Structural modeling indicates OvNR-2 possesses a ligand-binding cavity suitable for steroids.
- OvNR-2 mRNA is specifically expressed in intrauterine microfilariae.
- The recombinant OvNR-2 protein is recognized by antibodies from a majority of infected individuals.
Conclusions:
- OvNR-2 is a steroid-binding nuclear receptor expressed in a specific developmental stage of Onchocerca volvulus.
- OvNR-2 represents a potential target for diagnostic tools or therapeutic interventions against Onchocerca volvulus infection.