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Discovery of fungal surface NADases predominantly present in pathogenic species.

<div class='caption-title'>Identification of fungal conidial NADases.</div>
<div class='caption-title'>AfNADase is a pure NAD(P)+ glycohydrolase.</div>
<div class='caption-title'>Crystal structure of AfNADase.</div>
Strømland Ø, Kallio JP, Pschibul A, Skoge RH, Harðardóttir HM, Sverkeli LJ, Heinekamp T, Kniemeyer O, Migaud M, Makarov MV, Gossmann TI, Brakhage AA, Ziegler M
OpenAccess logo Nat Commun 12 1631 (2021)
Related entries: 6yge, 6ygg

Cited: 7 times
EuropePMC logo PMID: 33712585

Abstract

Nicotinamide adenine dinucleotide (NAD) is a key molecule in cellular bioenergetics and signalling. Various bacterial pathogens release NADase enzymes into the host cell that deplete the host's NAD+ pool, thereby causing rapid cell death. Here, we report the identification of NADases on the surface of fungi such as the pathogen Aspergillus fumigatus and the saprophyte Neurospora crassa. The enzymes harbour a tuberculosis necrotizing toxin (TNT) domain and are predominately present in pathogenic species. The 1.6 Å X-ray structure of the homodimeric A. fumigatus protein reveals unique properties including N-linked glycosylation and a Ca2+-binding site whose occupancy regulates activity. The structure in complex with a substrate analogue suggests a catalytic mechanism that is distinct from those of known NADases, ADP-ribosyl cyclases and transferases. We propose that fungal NADases may convey advantages during interaction with the host or competing microorganisms.

Articles - 6ygf mentioned but not cited (3)

  1. Discovery of fungal surface NADases predominantly present in pathogenic species. Strømland Ø, Kallio JP, Pschibul A, Skoge RH, Harðardóttir HM, Sverkeli LJ, Heinekamp T, Kniemeyer O, Migaud M, Makarov MV, Gossmann TI, Brakhage AA, Ziegler M. Nat Commun 12 1631 (2021)
  2. Novel Calcium-Binding Motif Stabilizes and Increases the Activity of Aspergillus fumigatus Ecto-NADase. Ferrario E, Kallio JP, Strømland Ø, Ziegler M. Biochemistry 62 3293-3302 (2023)
  3. Rhs NADase effectors and their immunity proteins are exchangeable mediators of inter-bacterial competition in Serratia. Hagan M, Pankov G, Gallegos-Monterrosa R, Williams DJ, Earl C, Buchanan G, Hunter WN, Coulthurst SJ. Nat Commun 14 6061 (2023)


Reviews citing this publication (1)

  1. Emergence of the fungal immune system. Daskalov A. iScience 26 106793 (2023)

Articles citing this publication (3)

  1. Enzymatic and Chemical Syntheses of Vacor Analogs of Nicotinamide Riboside, NMN and NAD. Sverkeli LJ, Hayat F, Migaud ME, Ziegler M. Biomolecules 11 1044 (2021)
  2. Antigen specificity and cross-reactivity drive functionally diverse anti-Aspergillus fumigatus T cell responses in cystic fibrosis. Schwarz C, Eschenhagen P, Schmidt H, Hohnstein T, Iwert C, Grehn C, Roehmel J, Steinke E, Stahl M, Lozza L, Tikhonova E, Rosati E, Stervbo U, Babel N, Mainz JG, Wisplinghoff H, Ebel F, Jia LJ, Blango MG, Hortschansky P, Brunke S, Hube B, Brakhage AA, Kniemeyer O, Scheffold A, Bacher P. J Clin Invest 133 e161593 (2023)
  3. Structural basis of antiphage immunity generated by a prokaryotic Argonaute-associated SPARSA system. Zhen X, Xu X, Ye L, Xie S, Huang Z, Yang S, Wang Y, Li J, Long F, Ouyang S. Nat Commun 15 450 (2024)


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