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Discovery of fungal surface NADases predominantly present in pathogenic species
DOI:
10.1038/s41467-021-21307-z
Authors:
Oyvind
Stromland
(University of Bergen)
,
Juha P.
Kallio
(University of Bergen)
,
Annica
Pschibul
(Hans Knöll Institute)
,
Renate H.
Skoge
(University of Bergen)
,
Hulda M.
Harðardóttir
(University of Bergen)
,
Lars J.
Sverkeli
(University of Bergen)
,
Thorsten
Heinekamp
(Hans Knöll Institute)
,
Olaf
Kniemeyer
(Hans Knöll Institute)
,
Marie
Migaud
(University of South Alabama)
,
Mikhail V.
Makarov
(University of South Alabama)
,
Toni I.
Gossmann
(Bielefeld University; University of Sheffield)
,
Axel A.
Brakhage
(Hans Knöll Institute; Friedrich Schiller University Jena)
,
Mathias
Ziegler
(University of Bergen)
Co-authored by industrial partner:
No
Type:
Journal Paper
Journal:
Nature Communications
, VOL 12
State:
Published (Approved)
Published:
March 2021

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.
Journal Keywords: Fungal biology; Hydrolases; Pathogens; X-ray crystallography
Subject Areas:
Biology and Bio-materials,
Chemistry,
Medicine
Instruments:
I04-Macromolecular Crystallography
Other Facilities: P11 and P13 at PETRA III
Added On:
16/03/2021 14:57
Documents:
s41467-021-21307-z.pdf
Discipline Tags:
Pathogens
Health & Wellbeing
Biochemistry
Chemistry
Structural biology
Drug Discovery
Life Sciences & Biotech
Technical Tags:
Diffraction
Macromolecular Crystallography (MX)