6Y37

CCAAT-binding complex from Aspergillus nidulans with cccA DNA

6Y37 の概要

• エントリーDOI: 10.2210/pdb6y37/pdb
• 関連するPDBエントリー: 4G91 4G92
• 分子名称: HapB, Transcription factor HapC (Eurofung), CBFD_NFYB_HMF domain-containing protein, ... (7 entities in total)
• 機能のキーワード: transcription factor, heterotrimer, histone fold, protein:dna complex, transcription
• 由来する生物種: Aspergillus nidulans FGSC A4; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 47427.98

構造登録者

Groll, M.,Huber, E.M. (登録日: 2020-02-17, 公開日: 2020-05-27, 最終更新日: 2024-01-24)

主引用文献

Hortschansky, P.,Misslinger, M.,Morl, J.,Gsaller, F.,Bromley, M.J.,Brakhage, A.A.,Groll, M.,Haas, H.,Huber, E.M.
Structural basis of HapE P88L -linked antifungal triazole resistance in Aspergillus fumigatus .
Life Sci Alliance, 3:-, 2020

PubMed Abstract: Azoles are first-line therapeutics for human and plant fungal infections, but their broad use has promoted the development of resistances. Recently, a pan-azole-resistant clinical isolate was identified to carry the mutation P88L in subunit HapE of the CCAAT-binding complex (CBC), a conserved eukaryotic transcription factor. Here, we define the mechanistic basis for resistance in this isolate by showing that the HapE mutation interferes with the CBC's ability to bend and sense CCAAT motifs. This failure leads to transcriptional derepression of the gene, which encodes the target of azoles, the 14-α sterol demethylase Cyp51A, and ultimately causes drug resistance. In addition, we demonstrate that the CBC-associated transcriptional regulator HapX assists repression in low-iron environments and that this iron-dependent effect is lost in the HapE mutant. Altogether, these results indicate that the mutation HapE confers increased resistance to azoles compared with wt , particularly in low-iron clinical niches such as the lung.

PubMed: 32467317
DOI: 10.26508/lsa.202000729

実験手法

X-RAY DIFFRACTION (2.2 Å)