Discovery of fungal surface NADases predominantly present in pathogenic species.

Autor: Strømland Ø; Department of Biomedicine, University of Bergen, Bergen, Norway., Kallio JP; Department of Biomedicine, University of Bergen, Bergen, Norway., Pschibul A; Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany., Skoge RH; Department of Biological Sciences, University of Bergen, Bergen, Norway., Harðardóttir HM; Department of Biological Sciences, University of Bergen, Bergen, Norway., Sverkeli LJ; Department of Biomedicine, University of Bergen, Bergen, Norway.; Department of Biological Sciences, University of Bergen, Bergen, Norway., Heinekamp T; Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany., Kniemeyer O; Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany., Migaud M; Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA., Makarov MV; Mitchell Cancer Institute, University of South Alabama, Mobile, AL, USA., Gossmann TI; Department of Animal Behaviour, Bielefeld University, Bielefeld, Germany.; Department of Animal and Plant Sciences, University of Sheffield, Sheffield, UK., Brakhage AA; Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.; Institute of Microbiology, Friedrich Schiller University Jena, Jena, Germany., Ziegler M; Department of Biomedicine, University of Bergen, Bergen, Norway. mathias.ziegler@uib.no.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Mar 12; Vol. 12 (1), pp. 1631. Date of Electronic Publication: 2021 Mar 12.
DOI: 10.1038/s41467-021-21307-z
Abstrakt: 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 Ca 2+ -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.
Databáze: MEDLINE
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