TY - JOUR
T1 - The role of zinc in copper homeostasis of aspergillus fumigatus
AU - Kang, Suzie
AU - Seo, Hyewon
AU - Yun, Cheol Won
AU - Moon, Hee Soo
AU - Kwon, Joon Ho
AU - Park, Yong Sung
N1 - Funding Information:
Funding: This work was carried out with the support of the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. NRF-2018R1D1A1B07049119) and by a Korea University Grant.
PY - 2020/10/2
Y1 - 2020/10/2
N2 - Copper is an essential metal ion that performs many physiological functions in living organisms. Deletion of Afmac1, which is a copper-responsive transcriptional activator in A. fumigatus, results in a growth defect on aspergillus minimal medium (AMM). Interestingly, we found that zinc starvation suppressed the growth defect of the ∆afmac1 strain on AMM. In addition, the growth defect of the ∆afmac1 strain was recovered by copper supplementation or introduction of the CtrC gene into the ∆afmac1 strain. However, chelation of copper by addition of BCS to AMM failed to recover the growth defect of the ∆afmac1 strain. Through Northern blot analysis, we found that zinc starvation upregulated CtrC and CtrA2, which encode membrane copper transporters. Interestingly, we found that the conserved ZafA binding motif 5′-CAA(G)GGT-3′ was present in the upstream region of CtrC and CtrA2 and that mutation of the binding motif led to failure of ZafA binding to the upstream region of CtrC and upregulation of CtrC expression under zinc starvation. Furthermore, the binding activity of ZafA to the upstream region of CtrC was inversely proportional to the zinc concentration, and copper inhibited the binding of ZafA to the upstream region of CtrC under a low zinc concentration. Taken together, these results suggest that ZafA upregulates copper metabolism by binding to the ZafA binding motif in the CtrC promoter region under low zinc concentration, thus regulating copper homeostasis. Furthermore, we found that copper and zinc interact in cells to maintain metal homeostasis.
AB - Copper is an essential metal ion that performs many physiological functions in living organisms. Deletion of Afmac1, which is a copper-responsive transcriptional activator in A. fumigatus, results in a growth defect on aspergillus minimal medium (AMM). Interestingly, we found that zinc starvation suppressed the growth defect of the ∆afmac1 strain on AMM. In addition, the growth defect of the ∆afmac1 strain was recovered by copper supplementation or introduction of the CtrC gene into the ∆afmac1 strain. However, chelation of copper by addition of BCS to AMM failed to recover the growth defect of the ∆afmac1 strain. Through Northern blot analysis, we found that zinc starvation upregulated CtrC and CtrA2, which encode membrane copper transporters. Interestingly, we found that the conserved ZafA binding motif 5′-CAA(G)GGT-3′ was present in the upstream region of CtrC and CtrA2 and that mutation of the binding motif led to failure of ZafA binding to the upstream region of CtrC and upregulation of CtrC expression under zinc starvation. Furthermore, the binding activity of ZafA to the upstream region of CtrC was inversely proportional to the zinc concentration, and copper inhibited the binding of ZafA to the upstream region of CtrC under a low zinc concentration. Taken together, these results suggest that ZafA upregulates copper metabolism by binding to the ZafA binding motif in the CtrC promoter region under low zinc concentration, thus regulating copper homeostasis. Furthermore, we found that copper and zinc interact in cells to maintain metal homeostasis.
KW - Aspergillus fumigatus
KW - Copper
KW - CtrC
KW - ZafA
KW - Zinc
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U2 - 10.3390/ijms21207665
DO - 10.3390/ijms21207665
M3 - Article
C2 - 33081273
AN - SCOPUS:85092569533
VL - 21
SP - 1
EP - 15
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 20
M1 - 7665
ER -