Schizosaccharomyces pombe Grx4, Fep1, and Php4: In silico analysis and expression response to different iron concentrations

Alia Ebrahim; Manal A Alfwuaires; Mohammad H Abukhalil; Fawaz Alasmari; Fawad Ahmad; Rui Yao; Ying Luo; Ying Huang

doi:10.3389/fgene.2022.1069068

Schizosaccharomyces pombe Grx4, Fep1, and Php4: In silico analysis and expression response to different iron concentrations

Front Genet. 2022 Dec 7:13:1069068. doi: 10.3389/fgene.2022.1069068. eCollection 2022.

Authors

Alia Ebrahim¹, Manal A Alfwuaires², Mohammad H Abukhalil^{3

4}, Fawaz Alasmari⁵, Fawad Ahmad¹, Rui Yao¹, Ying Luo¹, Ying Huang¹

Affiliations

¹ Jiangsu Key Laboratory for Microbes and Genomics, School of Life Sciences, Nanjing Normal University, Nanjing, China.
² Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa, Saudi Arabia.
³ Department of Medical Analysis, Princess Aisha Bint Al-Hussein College of Nursing and Health Sciences, Al-Hussein Bin Talal University, Ma'an, Jordan.
⁴ Department of Biology, College of Science, Al-Hussein Bin Talal University, Ma'an, Jordan.
⁵ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Abstract

Due to iron's essential role in cellular metabolism, most organisms must maintain their homeostasis. In this regard, the fission yeast Schizosaccharomyces pombe (sp) uses two transcription factors to regulate intracellular iron levels: spFep1 under iron-rich conditions and spPhp4 under iron-deficient conditions, which are controlled by spGrx4. However, bioinformatics analysis to understand the role of the spGrx4/spFep1/spPhp4 axis in maintaining iron homeostasis in S. pombe is still lacking. Our study aimed to perform bioinformatics analysis on S. pombe proteins and their sequence homologs in Aspergillus flavus (af), Saccharomyces cerevisiae (sc), and Homo sapiens (hs) to understand the role of spGrx4, spFep1, and spPhp4 in maintaining iron homeostasis. The three genes' expression patterns were also examined at various iron concentrations. A multiple sequence alignment analysis of spGrx4 and its sequence homologs revealed a conserved cysteine residue in each PF00085 domain. Blast results showed that hsGLRX3 is most similar to spGrx4. In addition, spFep1 is most closely related in sequence to scDal80, whereas scHap4 is most similar to spFep1. We also found two highly conserved motifs in spFep1 and its sequence homologs that are significant for iron transport systems because they contain residues involved in iron homeostasis. The scHap4 is most similar to spPhp4. Using STRING to analyze protein-protein interactions, we found that spGrx4 interacts strongly with spPhp4 and spFep1. Furthermore, spGrx4, spPhp4, and spFep1 interact with spPhp2, spPhp3, and spPhp5, indicating that the three proteins play cooperative roles in iron homeostasis. At the highest level of Fe, spgrx4 had the highest expression, followed by spfep1, while spphp4 had the lowest expression; a contrast occurred at the lowest level of Fe, where spgrx4 expression remained constant. Our findings support the notion that organisms develop diverse strategies to maintain iron homeostasis.

Keywords: Fep1; Grx4; Php4; Schizosaccharomyces pombe; iron homeostasis.