Study of Candida albicans Hap43 and CCAAT-binding complex in iron homeostasis

白色念珠菌Hap43及CCAAT-結合複合物參與鐵平衡之研究

葉雅玲(Ya-Ling Ye)

指導教授 ： 藍忠昱

國立清華大學/生命科學院/分子與細胞生物研究所/碩士(2011年)

摘要

Candida albicans is an opportunistic pathogen, which is a part of normal flora (commensal) in healthy individuals and can become invasive in immunocompromised patients with a 44% mortality rate. Iron is a significant cofactor for many enzymes that are essential for cellular functions both in human and C. albicans. Iron uptake during infection is thus considered as a virulence contributor to this fungus. In the previous study, we found that C. albicans Hap43 is essential for its growth under the low-iron condition which mimics the environment within the host. Deletion of HAP43 also attenuates the virulence of C. albicans in a mouse model of infection. In this study, we further characterized the functional domains of Hap43 to understand the molecular mechanism of iron-responsive gene regulation by Hap43. In silico domain prediction and sequence alignment of Hap43 showed that Hap43 contains a CCAAT-binding complex (CBC) binding domain (CBD), a bZIP domain, a NES peptide, a NLS peptide, and three cysteine-rich domains. The putative CBD and bZIP domains are both demonstrated to be essential for Hap43 normal function. We also proved that Hap43 possesses a C-terminal repression domain critical for gene repression in response to iron limitation. In addition, we displayed that the activity of the repression domain is regulated by a regulatory domain (RD) which is located between the two cysteine-rich domains. Furthermore, we provided the evidences that Hap43 cooperates with CBC to repress the gene expression and mediate the flavinogenesis under the low-iron condition. Together, CBC has general biological functions, while Hap43 functions mainly in the iron-limited condition.

關鍵字

白色念珠菌

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