Author Correction: Discovery of fungal surface NADases predominantly present in pathogenic species

Abstract

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-22476-7

Evolution of fungal tuberculosis necrotizing toxin (TNT) domain‐containing enzymes reveals divergent adaptations to enhance NAD cleavage

“…The inspection of the sequences revealed consistent differences at the N‐ and C‐terminal regions of the predicted proteins, following the branches of the tree (Figure 3a ). The residues previously identified to form a Ca 2+ binding motif important for dimer stabilization in Af NADase (Asp219, Glu220 and Glu223) (Ferrario et al, 2023 ; Strømland et al, 2021 ) are conserved only in the Eurotiomycetes class (Clade IV; Figure 3a , highlighted in red). In the clade containing sequences from Sordariomycetes as well as Leotiomycetes, mostly Fusarium and Botrytis genus, respectively, we note the strong conservation of cysteine residues in both the N‐ and C‐terminal region of the NADase (Clade I; Figure 3a , highlighted in green).…”

“…The pathogenic mechanism of the tuberculosis necrotizing toxin (TNT) from Mycobacterium tuberculosis ( Mtb ) has been demonstrated to be based on its catalytic activity as an NAD glycohydrolase (Figure 1a ) (Danilchanka et al, 2014 ; Sun et al, 2015 ). In a recent study, we discovered NADase activity on the surface of another deleterious pathogen, the fungus Aspergillus fumigatus (Strømland et al, 2021 ). The causative protein was identified, and functionally and structurally characterized, which led to the recognition that the catalytic domain is also of the TNT family albeit highly divergent, thus suggesting a common evolutionary origin (Figure 1b ).…”

“…In contrast, A. fumigatus lacks a homolog of the IFT, and the pathway through which Af NADase reaches the cell exterior involves the secretory pathway, which would protect the cytosol from its catalytic activity. Sequence comparisons have indicated that there are other species in both the bacterial domain and the fungal kingdom that harbor TNT‐encoding genes (Strømland et al, 2021 ). However, a comprehensive analysis of the phylogenetic distribution of TNT domain proteins is lacking and their occurrence in fungi and bacteria has not been systematically studied.…”

“…Af NADase exists as a homodimer (Strømland et al, 2021 ) and the two protomers are associated in a head‐to‐tail configuration, that is, the N‐terminus of one protomer is in close vicinity to the C‐terminus of the other protomer. The stability of the dimer is intricately regulated by a calcium ion binding motif located at the dimerization interface between the two protomers.…”

“…Remarkably, the Ca 2+ binding motif also governs the enzyme's turnover rate, via a long‐range network of interactions that influence the active site's conformation upon Ca 2+ binding or release (Ferrario et al, 2023 ). In this regard, it is surprising that the Ca 2+ binding motif appears to be a unique trait in the order of Eurotiales (containing Aspergillus species) (Strømland et al, 2021 ), while, according to initial sequence comparisons, the structures of fungal NADases in other orders would be predicted to be otherwise highly similar. Given the functional importance of this motif in Af NADase, its predicted absence in other fungal NADases is puzzling.…”