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Characterization of a heme-protein responsive to hypoxia in Paracoccidioides brasiliensis.
Fungal Genetics and Biology ( IF 2.4 ) Pub Date : 2020-08-19 , DOI: 10.1016/j.fgb.2020.103446
Lucas Nojosa Oliveira 1 , Relber Aguiar Gonçales 2 , Marielle Garcia Silva 1 , Raisa Melo Lima 1 , Mariana Vieira Tomazett 1 , Juliana Santana de Curcio 1 , Juliano Domiraci Paccez 1 , Vanessa Rafaela Milhomem Cruz-Leite 1 , Fernando Rodrigues 2 , Patrícia de Sousa Lima 1 , Maristela Pereira 1 , Célia Maria de Almeida Soares 1
Affiliation  

Oxygen is fundamental to the life of aerobic organisms and is not always available to Paracoccidioides cells. During the life cycle stages, reduced oxygen levels directly affect general metabolic processes and oxygen adaptation mechanisms may play a fundamental role on fungal ability to survive under such condition. Heme proteins can bind to oxygen and participate in important biological processes. Several fungi, including Paracoccidioides, express a heme-binding globin (fungoglobin - FglA) presumable to regulate fungal adaptation to hypoxia. However, the characterization of fungoglobin in Paracoccidioides spp. has not yet been performed. In this study, we predicted the structure of fungoglobin and determined its level of expression during hypoxic-mimetic conditions. Genomic screening revealed that the fungoglobin gene is conserved in all species of the Paracoccidioides genus. Molecular modeling showed biochemical and biophysical characteristics that support the hypothesis that FglA binds to the heme group and oxygen as well. The fungoglobin transcript and proteins are expressed at higher levels at the early treatment time, remaining elevated while oxygen is limited. A P. brasiliensis fglA knockdown strain depicted reduced growth in hypoxia indicating that this protein can be essential for growth at low oxygen. Biochemical analysis confirmed the binding of fungoglobin to heme. Initial analyzes were carried out to establish the relationship between FlglA and iron metabolism. The FglA transcript was up regulated in pulmonary infection, suggesting its potential role in the disease establishment. We believe that this study can contribute to the understanding of fungal biology and open new perspectives for scientific investigations.



中文翻译:

巴西副球孢子虫对缺氧反应的血红素蛋白的表征。

氧气是需氧生物生命的基础,但并不总是可用于副球孢子菌细胞。在生命周期阶段,氧气水平降低直接影响一般代谢过程,氧气适应机制可能对真菌在这种条件下的生存能力起着根本性的作用。血红素蛋白可以与氧气结合并参与重要的生物过程。几个真菌,包括副球孢子,表达血红素结合珠蛋白(fungoglobin - FglA)推测调节真菌适应缺氧。然而,副球孢子菌中真菌红蛋白的特征属 尚未执行。在这项研究中,我们预测了真菌红蛋白的结构并确定了其在缺氧模拟条件下的表达水平。基因组筛选显示,真菌红蛋白基因在副球孢子菌属的所有物种中都是保守的。分子模型显示的生化和生物物理特征支持 FglA 也与血红素组和氧结合的假设。真菌红蛋白转录物和蛋白质在治疗早期以较高水平表达,在氧气有限的情况下保持升高。A P. brasiliensis fglA敲低菌株描述了缺氧条件下的生长减少,表明这种蛋白质对于低氧条件下的生长至关重要。生化分析证实了真菌红蛋白与血红素的结合。进行初步分析以确定 FlglA 与铁代谢之间的关系。FglA 转录物在肺部感染中上调,表明其在疾病建立中的潜在作用。我们相信这项研究有助于理解真菌生物学并为科学调查开辟新的视角。

更新日期:2020-09-01
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