Functional analysis of predicted DHHC cysteine-rich domain palmitoyl acyltransferase AkrA/ SidR in Aspergilli

Yuanwei Zhang, Jinxing Song, Lina Gao, Qingqing Zheng, Ling Lu

Author address: 

Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Microbiology; College of Life Sciences, Nanjing Normal University, Nanjing, 210023, China

Abstract: 

Protein palmitoylation is a post-translational modification process that is important in regulation of membrane-protein interactions and intracellular protein stability. In mammalian cells, the Golgi-specific zinc finger protein palmitoyl acyltransferase mediates the palmitoylation and posttranslational modification of many protein substrates. However, the machinery as well as their components involved in protein palmitoylation has remained elusive in Aspergilli. In this study, human palmitoyl acyltransferases homologs AkrA in Aspergillus nidulans and SidR in Aspergillus fumigatus have been characterized respectively using conditional and null deletion mutants. Notably, both of AkrA and SidR contain five predicted transmembrane domains that possibly are reminiscent of the membrane receptor or transporter. In addition, either of AkrA or SidR possesses a cytoplasmic DHHC cysteine-rich domain at the C-terminus, which may confer palmitoyl acyltransferase activity. Moreover, deletion or depletion akrA or sidR showed significantly smaller colony sizes, and the remarkably reduction of conidiospores under the low-calcium condition. Interestingly, this growth defect can be significantly suppressed by adding extracellular calcium, suggesting that hyphal growth and conidiation depends on the function of AkrA/SidR when strains faced with limited extracellular calcium. Most importantly, the defect of AkrA displayed a significant hyper-susceptibility to the azole drug -Itraconazole or Voriconazole but showed the more resistance to cell wall-perturbing agents. These findings suggest that AkrA or SidR may represent a viable and completely unexplored avenue to be a fungicide target in the Aspergilli. Ongoing studies will focus on how AkrA/SidR functions by affecting the protein palmitoylation to regulate calcium signaling pathway and the resistance to azole.
2013

abstract No: 

NULL

Full conference title: 

Asian Mycological Congress 2013 and the 13th International Marine and Freshwater Mycology Symposium
    • AMC 2013