Biology Faculty Articles
Title
Developing a Physical Model of HigB Toxin and its Endonuclease Cleavage Mechanism
Document Type
Article
Publication Date
4-1-2019
Publication Title
The FASEB Journal
ISSN
1530-6860
Volume
33
Issue/No.
1 Supplement
Abstract
The CREST (Connecting Researchers, Educators, and STudents) team at Nova Southeastern University created a physical model depicting the mechanism of endonuclease cleavage by the HigB protein as described in the literature. The proteins, toxin HigB and antitoxin HigA, are part of a type II toxin-antitoxin system that cleaves ribosome-bound mRNAs in bacteria. Chemical or physical stresses, such as extreme temperatures and lack of nutrients, lead to antitoxin degradation that releases HigB. Temporary inhibition of growth by HigB allows cells to more efficiently utilize current resources. Although HigB is referred to as a toxin, it is not inherently detrimental and can be beneficial to cellular survival. Bacteria that use this mechanism include Escherichia coli, Pseudomonas aeruginosa, and Proteus vulgaris. As such, HigB is of clinical interest due to its contribution in prolonging bacterial infections through antibiotic tolerance (persistence). When cells are not in a stressed state, HigA binds to and inactivates HigB, allowing growth and translation to proceed. Details of HigB in complex with the ribosome as well as residues important for mRNA cleavage were found in the Protein Data Bank file, 4ZSN, and imported into Jmol, a protein visualization software. The 4ZSN file consisted of several nucleic acid and protein bundles; Bundle 1 was examined in more detail. Specific program commands were developed to manipulate the original file into a format that was later 3-D printed to create an instructional molecular model, which was funded in part by NSF-DUE 1725940 for the CREST Project. This model highlights the ribosomal proteins, ribosomal RNA, and HigB along with its residues that are essential for mRNA cleavage. The N and C termini of the HigB protein were also indicated. This molecular model can be used to explain how ribosome-dependent proteins (HigB) target ribosome-bound mRNAs in bacterial systems. Providing a 3-D tool allows students to engage actively in understanding the complex process of endonuclease cleavage.
Additional Comments
This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
NSUWorks Citation
Chabbra, Alesa; Carolina Alzamora; Helana Ghali; Marina Handal; Mahima Kathiria; Alexander Jakub Martinek; Jenny Nguyen; Chandni Patel; Shreja Patel; Antoine Pham; and Emily F. Schmitt Lavin. 2019. "Developing a Physical Model of HigB Toxin and its Endonuclease Cleavage Mechanism." The FASEB Journal 33, (1 Supplement). https://nsuworks.nova.edu/cnso_bio_facarticles/959
Comments
NSF grant #: DUE 1725940